1. Extracellular vesicles: Roles in oocytes and emerging therapeutic opportunities.
期刊:Chinese medical journal
日期:2025-04-07
DOI :10.1097/CM9.0000000000003578
ABSTRACT:The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
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3区Q1影响因子: 2.3
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2. Impact of Curcumin on Frozen Bovine Sperm Quality and In Vitro Bovine Oocyte Maturation.
期刊:Veterinary sciences
日期:2025-05-05
DOI :10.3390/vetsci12050441
This study aimed to analyze the effect of curcumin on the antioxidant properties and fertility of freeze-thawed bovine spermatozoa and bovine oocytes. In this study, curcumin concentrations of 0, 5, 10, 25, and 50 µM were added bovine sperm cryopreservation solution and oocyte IVM medium to assess sperm quality, antioxidant properties, oocyte maturation, IVF rate, and embryonic development. The results demonstrated that adding curcumin to the cryopreservation solution significantly improved the viability, motility, and acrosome integrity of bull sperm after freezing and thawing ( < 0.05). The addition of 25 µM curcumin resulted in the best sperm quality. Analysis of antioxidant capacity showed that 25 µM curcumin significantly increased the activities of MMP and antioxidant enzymes, such as CAT, SOD, and GSH-PX, and lowered the levels of MDA and ROS ( < 0.05). Adding curcumin to the in vitro maturation medium notably enhanced the maturation rate and decreased DNA fragmented nuclei of bovine oocytes ( < 0.05), with optimal outcomes observed at 25 and 50 µM curcumin. Totals of 25 and 50 µM curcumin markedly elevated GSH and MMP ( < 0.05), reduced ROS and malondialdehyde concentrations ( < 0.05), and significantly enhanced fertilization rates and blastocyst formation ( < 0.05). In conclusion, incorporating curcumin into both the bovine semen cryopreservation solution and the oocyte IVM medium significantly improved the quality of frozen-thawed sperm, antioxidant activity, oocyte maturation, IVF rate, and embryonic development.
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3区Q1影响因子: 5.3
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3. The role of quercetin in NLRP3-associated inflammation.
期刊:Inflammopharmacology
日期:2024-09-22
DOI :10.1007/s10787-024-01566-0
Quercetin is a natural flavonoid that is widely found in fruits and vegetables. As an important flavonoid, it exhibits a wide range of biological activities, including antioxidant, anti-inflammatory, antiviral, immunomodulatory, and analgesic activities. Quercetin exerts powerful antioxidant activity by regulating glutathione, enzyme activity, and the production of reactive oxygen species (ROS). Quercetin exerts powerful anti-inflammatory effects by acting on the Nod-like receptor protein 3 (NLRP3) inflammasome. In diabetes, quercetin has been shown to improve insulin sensitivity and reduce high blood sugar level, while, in neurological diseases, it potentially prevents neuronal degeneration and cognitive decline by regulating neuroinflammation. In addition, in liver diseases, quercetin may improve liver inflammation and fibrosis by regulating the NLRP3 activity. In addition, quercetin may improve inflammation in other diseases based on the NLRP3 inflammasome. With this background, in this review, we have discussed the progress in the study on the mechanism of quercetin toward improving inflammation via NLRP3 inflammasome in the past decade. In addition, from the perspective of quercetin glycoside derivatives, the anti-inflammatory mechanism of hyperoside, rutin, and isoquercetin based on NLRP3 inflammasome has been discussed. Moreover, we have discussed the pharmacokinetics of quercetin and its nanoformulation application, with the aim to provide new ideas for further research on the anti-inflammatory effect of quercetin and its glycoside derivatives based on NLRP3 inflammasome, as well as in drug development and application.
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3区Q1影响因子: 2.7
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4. Impact of low versus high oxygen tension on human oocyte maturation during biphasic capacitation IVM (CAPA-IVM).
期刊:Journal of assisted reproduction and genetics
日期:2025-03-29
DOI :10.1007/s10815-025-03459-9
PURPOSE:This study investigated the impact of low versus high oxygen tension on the oocyte maturation rate in biphasic CAPA-IVM. METHODS:A sibling oocyte pilot study of cumulus-oocyte complexes (COCs) from participants with polycystic ovary syndrome was performed at an academic IVF center in Vietnam from November 2023 to May 2024. At collection, COCs were allocated to undergo CAPA-IVM culture with low oxygen tension (5%) or high oxygen tension (20%). Culture of COCs took place in two benchtop incubators, each equipped with commercial mix-gas bottles to establish the respective oxygen conditions. The primary outcome was the oocyte maturation rate. Secondary outcomes were rates of two-pronuclei fertilization, day-3 embryos, blastocyst formation, and good-quality embryos. RESULTS:A total of 554 COCs from 20 participants were assigned to the low oxygen (276 COCs) or high oxygen (278 COCs) tension groups. The oocyte maturation rate was significantly lower in the low oxygen tension versus high oxygen tension group (53.6% vs. 65.8%, risk ratio 0.81, 95% confidence interval 0.71-0.94; p=0.004). The two-pronuclei fertilization rate was significantly lower in the low oxygen tension versus high oxygen tension group (61.5% vs. 72.7%, p=0.03). Numbers of day-3 embryos, blastocysts, and good-quality blastocysts were slightly, but not significantly, lower in the low oxygen tension group compared with the high oxygen tension group. CONCLUSIONS:Low oxygen tension of 5% during both steps of biphasic CAPA-IVM reduced the number of matured oocytes and 2-pronuclei fertilized oocytes compared with the use of high oxygen tension (20%) during CAPA-IVM.
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3区Q1影响因子: 4.8
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5. Ginsenoside Re ameliorates thioacetamide-induced acute liver injury through inhibiting autophagy-NLRP3 inflammasome pathway.
期刊:Frontiers in pharmacology
日期:2025-06-20
DOI :10.3389/fphar.2025.1592203
Background:Ginsenoside Re (G-Re), a unique ginsenoside almost exclusively found in Araliaceae plants, is a promising therapeutic agent for attenuating liver injury. This study aims to investigate the liver-protective effects of G-Re and the underlying mechanisms in acute liver injury models. Methods:Male C57BL/6 mice were intraperitoneally injected with various agents induce the acute liver injury model after pre-treatment with G-Re (5-20 mg/kg, oral gavage). Additionally, the phosphoinositide 3-kinases (PI3K) inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor RAPA were co-administered with G-Re in the thioacetamide (TAA)-induced rat hepatic stellate cell line (HSC-T6) to explore the mechanisms associated with G-Re. Results:G-Re at (20 mg/kg) protected liver against thioacetamide (TAA), ethanol, acetaminophen, and D-Galactosamine-induced liver injury in C57BL/6 mice. G-Re reduced serum levels of aspartate aminotransferase (AST) from 151.98 to 40.24 U/L and alanine aminotransferase (ALT) from 392.04 to 49.43 U/L. Both and studies consistently showed that G-Re decreased mRNA expression levels of key pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Additionally, G-Re dose-dependently downregulated the protein expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate specific proteinase -1 (caspase-1), interleukin-18 (IL-18), and IL-1β. In addition, our results suggested that the suppression of autophagy by G-Re may play a crucial role in its ability to inhibit the NLRP3 inflammasome. Notably, this regulatory effect on autophagy appears to be mediated through the phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR signaling pathway). G-Re inhibits autophagy in both cellular and animal models by downregulating the expression of light chain 3-II (LC3-II), Beclin-1, and sequestosome-1 (p62) through this pathway. Furthermore, the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin (RAPA) were shown to partially reverse the inhibitory effects of G-Re on autophagy and inflammation in HSC-T6 cells. These results further support the notion that reactivation of autophagy can counteract G-Re-mediated suppression of NLRP3 and caspase-1 expression. Conclusion:This study highlights G-Re as a promising therapeutic candidate for liver injury, acting through inhibition of autophagy and inflammation via the PI3K/AKT/mTOR signaling pathway.
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2区Q1影响因子: 4.8
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6. Hypoxia Regulates the Proliferation and Apoptosis of Coronary Artery Smooth Muscle Cells Through HIF-1α Mediated Autophagy in Yak.
期刊:Biomolecules
日期:2025-02-10
DOI :10.3390/biom15020256
Cell proliferation and migration mediated by hypoxia-inducible factor-1α (HIF-1α) are important processes of hypoxic cardiac vascular remodeling. HIF-1α also regulates the physiological hypoxic adaptation of the coronary artery in the yak heart, but the potential mechanism remains to be completely elucidated. In this study, coronary artery proliferation increased with age and hypoxia adaptation time. In vitro analysis showed that hypoxia can promote the proliferation of coronary vascular smooth muscle cells (CASMCs). Meanwhile, HIF-1α plays an important role in the regulation of proliferation and migration under hypoxia. Autophagy regulates cell proliferation and migration to participate in hypoxia adaptation in plateau animals. Here, the level of autophagy increased significantly in yak coronary arteries with age and was regulated by HIF-1α-mediated hypoxia. In addition, autophagy could also mediate the hypoxic effect on the proliferation and migration of CASMCs. In summary, the results revealed that the increase in yak heart coronary artery thickening with age increases vascular smooth muscle cell proliferation and migration, mainly achieved through hypoxia-mediated HIF-1α-regulated autophagy. These results contribute to understanding how the heart adapts to life in a hypoxic environment.
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3区Q2影响因子: 3.7
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7. Luteolin Protects against Vascular Calcification by Modulating SIRT1/CXCR4 Signaling Pathway and Promoting Autophagy.
期刊:The AAPS journal
日期:2024-10-22
DOI :10.1208/s12248-024-00982-y
Vascular calcification (VC) is a common pathological manifestation of atherosclerosis, hypertension, diabetes vascular disease, vascular injury, chronic kidney disease and aging, which is mainly manifested as increased stiffness of the vascular wall. Oxidative stress and autophagy dysfunction are key factors in the pathogenesis of vascular calcification, but the specific mechanisms and the therapeutic strategy of vascular calcification have not been clarified. In the present study, Sirtuin 1 (SIRT1) was screened as the therapeutic targets for vascular calcification by the bioinformatics. SIRT1 is a nicotinamide adenine dinucleotide, which plays an important role in inhibiting oxidative stress and promoting autophagy. Luteolin (LUT), a kind of natural tetrahydroxyl flavonoid, exists in many plants and has many pharmacological effects such as anti-oxidation and anti-apoptosis. We have reported that luteolin has certain anti-osteoporosis effects in the previous study, and it is accepted that the development of vascular calcification is similar to bone formation, indicating that luteolin may also resist vascular calcification. And luteolin is known to activate SIRT1 to some extent. Moreover, the molecular docking analysis predicted that SIRT1 could bind directly to luteolin. Therefore, the purpose of this study was to investigate the potential role of luteolin in inhibiting oxidative stress and promoting autophagy during vascular calcification via modulating SIRT1 expression. The results showed that luteolin significantly improved vascular calcification induced by a high-fat diet (HFD) and vitamin D in rats in vivo. In addition, luteolin significantly repressed the formation of mineralized nodules and ALP activity in HO-treated A7r5 cells. Luteolin reduced the level of MDA, LDH and ROS generation, inhibited the protein expression of cleaved caspase-3, cleaved caspase-9, β-catenin and BMP-2 in the aortic tissue of the rat and rat smooth muscle cells (A7r5) treated with hydrogen peroxide. At the same time, luteolin could promote the expression of autophagy related proteins. Moreover, luteolin also produced effects to increase the protein expression levels of SIRT1 more than 2 times both in vivo and in vitro. In terms of mechanism, luteolin attenuated vascular calcification by inhibiting oxidative stress and improving autophagy level, via modulating SIRT1 / CXCR4 signaling pathway. In conclusion, this experiment for the first time revealed that LUT protected against VC via modulating SIRT1 / CXCR4 signaling pathway to promote autophagy and inhibit vascular calcification and may be developed as a new therapeutic agent for vascular calcification and atherosclerosis.
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3区Q1影响因子: 3.9
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8. Long non-coding RNA NEAT1 promotes colorectal cancer progression via interacting with SIRT1.
期刊:Scientific reports
日期:2025-02-15
DOI :10.1038/s41598-025-90416-2
Nuclear-enriched abundant transcript 1 (NEAT1), a long noncoding RNA, is found to be significantly dysregulated in different types of cancer, including colorectal cancer (CRC). Nevertheless, there is still much to learn about the precise functions and processes of NEAT1 in the progression of CRC. Using The Cancer Genome Atlas (TCGA) database and 50 CRC specimens from the First Affiliated Hospital of Dali University, we assessed the expression of NEAT1 to determine its clinical impact. Through gene set enrichment analysis (GSEA), Cancer Single-cell State Atlas (CancerSEA), and immune infiltration studies, we elucidated key functions of NEAT1. We utilized Cell Counting Kit-8 (CCK8), wound healing, and Transwell assays to investigate the role of NEAT1 in the progression of CRC. Through the use of GSEA and immunohistochemistry, additional investigations were conducted to unveil the downstream targets of NEAT1 and gain insights into their regulatory dynamics. Our in vitro studies confirmed the regulatory role of NEAT1 in CRC. Findings indicate that increased NEAT1 expression correlates with adverse outcomes in colorectal tissues. In the CRC model, reduced levels of NEAT1 lead to reduced cell proliferation, invasion, and migration. Additionally, NEAT1 influenced immune cell infiltration in CRC and functioned as an oncogene by upregulating Sirtuin 1 (SIRT1) expression. This study demonstrates that NEAT1 promotes CRC progression and metastasis through a SIRT1-mediated mechanism, suggesting its potential as a prognostic biomarker and therapeutic target for CRC.
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2区Q1影响因子: 5.4
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9. Mechanism of arsenic regulation of mitochondrial damage and autophagy induced synaptic damage through SIRT1 and protective effect of melatonin in HT22 cell.
期刊:Chemico-biological interactions
日期:2025-03-11
DOI :10.1016/j.cbi.2025.111461
Arsenic (As), a widespread environmental pollutant, can induce severe neurological damage worldwide; however, the underlying mechanisms remain unclear. Sirtuin 1 (SIRT1) has been reported to exert neuroprotective effects against various neurological diseases by resisting mitochondrial damage and autophagy through deacetylation. In this study, we established a model of HT22 cells exposed to NaAsO and examined the levels of mitochondrial, autophagy, and synaptic damage in HT22 cells and HT22 cells with high expression of SIRT1 (pre-treated with the agonist SRT1720) 24 h after exposure. Our results suggest that NaAsO exposure induces down-regulation of SIRT1, causing mitochondrial damage and activation of autophagy, which in turn leads to synaptic damage. Notably, melatonin (Mel) intervention upregulated SIRT1 and attenuated mitochondrial damage and autophagy, restoring synaptic damage. In conclusion, the results of the present study indicate that As causes neurotoxicity by decreasing SIRT1 production, causing mitochondrial damage and activating autophagy, which provides fundamental data for further study of arsenic neurotoxicity. In addition, blocking this pathway attenuated the synaptic damage of arsenic exposure, which provides a new therapeutic avenue for arsenic neurotoxicity.
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2区Q1影响因子: 7.4
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10. Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis.
期刊:Redox report : communications in free radical research
日期:2025-05-13
DOI :10.1080/13510002.2025.2503130
BACKGROUND:Doxorubicin (DOX), a widely used chemotherapeutic agent, is limited in clinical application due to its dose-dependent cardiotoxicity. Therefore, it is crucial to explore alternative therapeutic molecules or drugs for mitigating DOX-induced cardiomyopathy (DIC). In this study aimed to explore underlying mechanisms of the cardioprotective effects of Kaempferol (KP) against DIC. METHODS:H9c2 cell-based DIC model were established to explore the pharmacological mechanism. The levels of mitochondrial membrane potential, mitochondrial ROS, mitochondrial Fe and lipid peroxidation were detected using JC-1, TMRE, Mito-SOX, Mito-Ferro Green and C11-BODIPY 581/591 probes. Furthermore, Western blot analysis measured the expression of key regulatory proteins, and NRF2-targeting siRNA was transfected into H9c2 cells. The nuclear translocation of NRF2 was assessed by immunofluorescence. RESULTS:Data revealed that KP mitigated DOX-induced mitochondrial damage and ferroptosis via reducing membrane potential, mitochondrial ROS/Fe², and regulating lipid metabolism. Mechanistically, Western blot analysis revealed that KP inhibited DOX-induced ferroptosis by activating NRF2/SLC7A11/GPX4 axis. Moreover, KP promoted the accumulation and nuclear translocation of NRF2 protein. CONCLUSION:These findings demonstrated that KP protected against DOX-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis. This provides novel insights into KP as a promising drug candidate for cardioprotection.
A well-regulated metabolism is crucial for optimal oocyte development and embryonic health. However, the metabolic framework governing oocyte maturation remains poorly understood. Using bovine oocytes as a model, we examined metabolomic and transcriptomic alterations during the transition from the germinal vesicle (GV) to the metaphase II (MII) stage. Our findings reveal distinct metabolic shifts, including suppressed β-oxidation combined with the accumulation of long-chain fatty acids (LCFAs). Notably, progesterone emerged as a key regulator of meiotic resumption through its influence on cAMP levels. We also observed enhanced glycolysis, moderate activation of the citric acid cycle (TCA cycle), and suppression of oxidative phosphorylation (OXPHOS), alongside reduced urea cycle flux and shifts in amino acid metabolism favoring glutamate synthesis. Intriguingly, discrepancies between metabolic and transcriptional activities in pathways such as the TCA cycle and nucleotide metabolism suggest asynchronous regulation. These findings provide a comprehensive multi-omics resource, advancing our understanding of the dynamic metabolic and transcriptional landscape during bovine oocyte maturation.
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1区Q1影响因子: 8.3
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12. Xiyangshen Sanqi Danshen granules attenuated D-gal-induced C57BL/6J mouse aging through the AMPK/SIRT1 signaling pathway.
期刊:Phytomedicine : international journal of phytotherapy and phytopharmacology
日期:2024-11-17
DOI :10.1016/j.phymed.2024.156213
BACKGROUND:Aging is a pressing global concern and is frequently accompanied by the emergence of many chronic diseases. Xiyangshen Sanqi Danshen granules (XSD) have antioxidant, anti-inflammatory and anti-fatigue functions, but the mechanism of their anti-aging effects is not clear. METHODS:This study elucidated the anti-aging mechanism and potentially active ingredients of XSD by performing transcriptomic analysis and network pharmacological analysis in a D-galactose (D-gal)-induced C57BL/6J mouse aging model. RESULTS:XSD improved learning and memory abilities while enhanced motor function in D-gal-induced aging mice, as shown by Morris water maze, passive avoidance test, and rotating rod test results. Additionally, XSD significantly increased the vascular pulse wave velocity (PWV), β-stiffness index and pressure strain elastic coefficient (EP), decreased carotid distensibility (CD) and decreased the expression levels of P53 and 8-OHdG in the common carotid arteries of D-gal mice. Transcriptome sequencing analysis identified that the AMPK/SIRT1 signaling pathway is the potential mechanism by which XSD attenuates aging. XSD also increased the protein levels of Ki67, AMPK, SIRT1 and the nuclear translocation of Nrf2 while decreased the protein levels of P21, P53, IL-18, 8-OHdG, nitrotyrosine, and COX-2 and the nuclear translocation of NF-κB p65 in the brains of D-gal-induced mice. The administration of the AMPK inhibitor and SIRT1 inhibitor hindered the anti-aging effect of XSD, as indicated by an elevation of 8-OHdG, COX-2, and nuclear translocation of NF-κB p65 ; and a decrease of Ki67 and the nuclear translocation of Nrf2. Network pharmacological analysis revealed that the potential active ingredients of XSD were quercetin, kaempferol, tanshinone IIA, isorhamnetin, ginsenoside F2, and cryptotanshinone. CONCLUSION:Collectively, XSD mitigated D-gal-induced aging in C57BL/6J mice through enhancing the AMPK/SIRT1 signaling pathway. This research provides potential drugs for anti-aging and also promotes the usage of the anti-aging effect of XSD.
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4区Q3影响因子: 1
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13. Mechanistic Insights into Salidroside's Mitochondrial Protection via AMPK/Sirt1/HIF-1α Pathway in Hypoxic HT22 Cells.
期刊:Journal of visualized experiments : JoVE
日期:2025-04-25
DOI :10.3791/66923
Salidroside (Sal), an active ingredient of Rhodiola crenulata (Hook. f. et Thoms.) H. Ohba has been found to exert mitochondrial protective effects by improving metabolism and enhancing the energy supply of brain cells under hypoxic conditions. However, its mechanism of action has not been fully clarified. In the present study, high-performance liquid chromatography was first employed to analyze the effects of Sal on nucleotide (ATP, ADP, and AMP) levels. The cellular thermal shift assay (CETSA), a widely used molecular interaction method for validating and quantifying drug target engagement in cells and tissues across different species, was then chosen to confirm the affinity of Sal for AMPK/Sirt1/HIF-1α pathway-related proteins. The results revealed that Sal increased ATP and ADP levels in hypoxic HT22 cells while reducing AMP levels. Moreover, Sal exhibited stable binding to AMPKα, p-AMPKα, Sirt1, and HIF-1α proteins. In conclusion, Sal may exert mitochondrial protective effects by modulating the AMPK/Sirt1/HIF-1α pathway to regulate nucleotide content. This study provides a methodological reference for nucleotide content analysis in cell samples and contributes to the identification and discovery of targets for compounds derived from traditional Chinese medicine.
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4区Q2影响因子: 3
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14. Protective effect of modafinil in bisphenol A-induced lung injury in rats: roles of SIRT1-dependent signaling pathways.
期刊:Immunopharmacology and immunotoxicology
日期:2025-03-03
DOI :10.1080/08923973.2025.2469218
BACKGROUND:Bisphenol A (BPA) is an industrial chemical used in manufacturing epoxy resins, polycarbonate plastics. We aimed to evaluate the possible protective effect of modafinil (MOD) in BPA-induced lung injury. MATERIALS AND METHODS:Twenty-four adult male albino Wistar rats were divided into four groups: Control group, MOD group: rats received modafinil 10 mg/kg/day for 4 weeks, BPA group: rats received Bisphenol A (500 mg/kg/day) for 4 weeks, MOD/BPA group: rats received MOD+ BPA. We measured arterial blood gas (ABG), malondialdehyde (MDA), nitric oxide (NOx), total antioxidant capacity (TAC), interlukin-1b (IL-1b), Sirtuin type 1 (SIRT1), Keap1, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), caspase-3 and forkhead-box transcription factor1 (FOXO1) levels, tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), apoptotic Bcl-2-associated protein x (Bax) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl2) and Heme Oxygenase-1 (HO-1) gene expression. Furthermore; histological changes, interlukin-6 (IL-6) immuno-expression were evaluated. RESULTS:BPA group showed significant increase in the partial pressure of carbon dioxide (PaCO2), MDA, NOx, IL-1b, keap1 and FOXO1, caspase-3 levels; TNF-α and NF-Κb, Bax and HO-1 gene expression, IL-6 exhibited a notable rise in immune-expression in the alveolar wall cells, interstitial cells, and infiltrating inflammatory cells. Moreover; it showed toxic histological changes of marked lung injury. Meanwhile, there is a significant decrease in the partial pressure of oxygen (PaO2), TAC, SIRT1, Nrf2 levels, and Bcl2 gene expression. MOD showed a significant improvement in all parameters. CONCLUSION:MOD possesses potent ameliorative effects against lung injury caused by BPA reducing oxidative stress, inflammatory process, and apoptosis through regulation of SIRT1/Nrf2 and SIRT1/FOXO1 signaling pathways.
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2区Q1影响因子: 6.1
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15. Gestational exposure to PNMC reduces offspring gamete numbers by disrupting oocyte meiosis and spermatogenesis.
期刊:Ecotoxicology and environmental safety
日期:2025-03-03
DOI :10.1016/j.ecoenv.2025.117980
3-Methyl-4-nitrophenol (PNMC) is a prevalent nitrophenolic endocrine disruptor found in pregnant women, with known effects on offspring growth and development. However, its impact on offspring fertility remains unexplored. This study investigates the effects of PNMC exposure during pregnancy on offspring fertility and the underlying mechanisms. Our fertility assessments revealed that PNMC exposure during pregnancy reduced the number of follicles and spermatozoa in offspring, though it did not affect their quality. In male offspring, PNMC exposure impaired spermatogenesis by reducing the number of Sertoli cells and spermatogonia. In female offspring, exposure disrupted the first meiotic prophase (MPI) of oocytes, leading to a reduced number of diplotene oocytes available for primordial follicle assembly. This depletion of primordial follicle reserve ultimately resulted in subfertility. Specifically, PNMC exposure hindered homologous recombination-mediated DNA double-strand break repair, triggering activation of the meiotic checkpoint and leading to MPI arrest. This arrested progression resulted in a depletion of diplotene oocytes. This is the first study to provide comprehensive evidence on the effects of PNMC exposure during pregnancy on offspring reproductive capacity, elucidating key pathways. These findings emphasize the need for stricter regulatory measures to limit PNMC exposure and offer new insights into the etiology of idiopathic oligozoospermia and diminished ovarian reserve.
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2区Q1影响因子: 2.5
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16. Exploring the impact of follicular fluid exosomes on porcine cumulus cell and oocyte function: Regulatory network analysis based on the ENSSSCG00000042788/ssc-miR-504/PDHA1 axis.
期刊:Theriogenology
日期:2025-06-24
DOI :10.1016/j.theriogenology.2025.117556
The development and maturation of mammalian oocytes are crucial stages in reproduction, directly influencing embryo health and the genetic quality of offspring. Follicular fluid serves as the microenvironment for oocyte development, with exosomes playing a key role in regulating the activities of cumulus cells and oocytes. However, the mechanisms governing porcine oocyte maturation remain incompletely understood. In this study, we conducted transcriptomic analysis on cumulus cells cultured with varying exosome concentrations and identified 334 differentially expressed long noncoding RNAs (lncRNAs). Functional enrichment analysis indicated that the differentially expressed lncRNAs may be involved in cumulus cell expansion, oocyte maturation, and embryo development. Through experiments such as transfection of mimics and inhibitor, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting (WB), we confirmed that lncRNA ENSSSCG00000042788 (lnc42788) regulates the expression of pyruvate dehydrogenase alpha 1 (PDHA1) by competitively binding to ssc-miR-504 (miR-504), forming a competing endogenous RNA (ceRNA) network. In summary, the lnc42788/miR-504/PDHA1 axis plays a key role in regulating the proliferation, apoptosis of porcine cumulus cells, and oocyte maturation.
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4区Q2影响因子: 2.1
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17. Season-specific effects of α-tocopherol supplementation during bovine oocyte maturation on embryo yield and quality.
期刊:Animal reproduction
日期:2025-05-09
DOI :10.1590/1984-3143-AR2024-0136
Elevated temperature-humidity index (THI) levels, common in subtropical summers, can impair bovine oocyte development by increasing reactive oxygen species (ROS) accumulation, leading to oxidative stress and reduced developmental competence. Alpha-tocopherol, a potent antioxidant, has the potential to mitigate these effects by scavenging ROS. However, its seasonal efficacy during bovine oocyte maturation (IVM) remains underexplored. This study evaluated the impact of 100 µM α-tocopherol supplementation during IVM on oocytes collected in spring (THI: 68.7±3) and summer (THI: 73±3) in Northern Uruguay. Oocytes underwent IVM, fertilization, and embryos were cultured until day 9 post-fertilization. Blastocysts were assessed for ROS levels, apoptosis, and the abundance of transcripts linked to development and oxidative stress. Results showed a season-specific response to α-tocopherol supplementation. While no significant effects were observed in spring, summer oocytes exhibited increased maturation, cleavage, and blastocyst rates, along with improved blastocyst quality characterized by reduced apoptosis and lower transcript levels. These findings indicate that α-tocopherol supplementation during IVM enhances oocyte developmental competence under heat stress conditions, supporting its potential as a strategy to mitigate oxidative damage and improve bovine embryo production during summer.
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2区Q1影响因子: 8.9
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18. BDNF secreted by mesenchymal stem cells improves aged oocyte quality and development potential by activating the ERK1/2 pathway.
期刊:Cell communication and signaling : CCS
日期:2025-03-23
DOI :10.1186/s12964-025-02137-8
BACKGROUND:Reduced oocyte quality is a key factor in age-related fertility decline, and there are no effective treatments available. The secretome of mesenchymal stem cells (MSC-sec) contains various bioactive factors and has the potential to improve oocyte quality. This study aimed to investigate the effective component and molecular mechanism of MSC-sec involved in improving oocyte quality from aged mice and humans. METHODS:Immunofluorescence and chromosome spread were performed to investigate the effects of secretome from human umbilical cord-MSC on spindle assembly and aneuploidy in aged mouse oocytes. Brain-derived neurotrophic factor (BDNF) and its neutralization antibody was supplemented in both in vitro and in vivo experiments to verify the effective component in MSC-sec. RNA-seq analysis was used to reveal the alterations in maternal mRNA degradation in aged mouse oocytes after MSC-sec treatment. In vitro culture of oocytes from aged women was also used to verify the effectiveness of BDNF in improving oocyte quality. RESULTS:MSC-sec treatment significantly increased first polar body emission, improved spindle assembly, promoted maternal RNA degradation, and reduced aneuploidy rate in aged mouse oocytes. While the addition of BDNF neutralization antibody blocked the effects of MSC-sec, BDNF alone also increased the oocyte quality from aged mice. Mechanistically, both MSC-sec and BDNF rescued the quality of aged mouse oocytes by activating the ERK1/2 signaling pathway to increase the expression of DAZL and BTG4. In situ injection of MSC-sec or BDNF into aged mouse ovaries significantly improved oocyte quality and early embryonic development. Finally, we demonstrated that BDNF treatment increased both the fertilization rate and blastocyst formation rate of aged human oocytes. CONCLUSION:These findings demonstrate that BDNF secreted by mesenchymal stem cells can improve the quality and development potential of oocytes from both aged mice and humans by activating the ERK1/2 signaling pathway, suggesting that it has the potential to mitigate age-related declines in oocyte quality.
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4区Q4影响因子: 1.4
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19. The role of sperm protein in mammal fertilization: insights into gamete adhesion, membrane fusion and oocyte activation.
期刊:Zygote (Cambridge, England)
日期:2025-05-13
DOI :10.1017/S0967199425000085
Globally, numerous infertile couples have been assisted by extensive research on mammalian fertilization and the rapid development of Assisted Reproductive Technology (ART). However, 5%-15% of the couples that are selected for in vitro fertilization (IVF) experience a total fertilization failure (TFF), where no zygotes develop despite oocytes and semen parameters appear to be normal. Notably, an essential early event in fertilization is the binding of spermatozoa to the oocyte's external envelope, which followed by the spermatozoa-oocyte fusion. Meanwhile, oocyte activation is a crucial cellular process necessary to block polyspermy and start the development of the zygote. Improper membrane fusion of gametes has been demonstrated to be one of the mechanisms of TFF. Moreover, considering the large amount of research on sperm proteins in recent years, thus in this review, we characterize the role and molecular mechanisms of sperm proteins in the three key processes of gamete adhesion and fusion and oocyte activation, which would provide a comprehensive understanding of the role of sperm proteins in fertilization in mammals and a favourable reference for future studies in assisted reproduction due to FF.
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2区Q1影响因子: 4.2
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20. Icariin attenuates oxidative stress via SIRT1/PGC-1α pathway in SAH mice.
期刊:Experimental neurology
日期:2025-05-08
DOI :10.1016/j.expneurol.2025.115303
Oxidative stress plays a pivotal role in the pathological response of subarachnoid hemorrhage (SAH). Icariin (ICA), with its potent antioxidant properties, exerts neuroprotective effects in stroke. This study investigated the beneficial effects of ICA on SAH-induced oxidative damage and its possible molecular mechanisms. The results indicated that ICA treatment improved both short-term and long-term neurobehavioral functions in mice with SAH. ICA significantly inhibited SAH-induced reactive oxygen species (ROS) generation and lipid peroxidation. Simultaneously, ICA restored the activity of the endogenous antioxidant enzyme system. Furthermore, ICA mitigated mitochondrial damage, improved mitochondrial morphology, further reduced neuronal apoptosis, and decreased brain edema following SAH. Mechanistically, ICA suppressed oxidative stress after SAH by activating Sirtuin 1 (SIRT1), subsequently upregulating the expression of PGC-1α. The SIRT1 inhibitor EX527 significantly inhibited ICA-induced SIRT1 activation and abolished the antioxidant and neuroprotective effects of ICA. In cellular experiments, ICA also inhibited ROS production and enhanced cell viability. These effects were associated with SIRT1 activation and were reversed by EX527 treatment. In conclusion, this study explored the protective effects of ICA against SAH-induced oxidative damage, suggesting that ICA could be a potential therapeutic agent for SAH.
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1区Q1影响因子: 11.3
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21. Fine particulate matter and its chemical constituents on oocyte quality in controlled ovarian hyperstimulation cycles: A prospective cohort study in China.
期刊:Journal of hazardous materials
日期:2025-06-28
DOI :10.1016/j.jhazmat.2025.139098
Previous studies have examined the association between fine particulate matter (PM) and female oocyte quality; however, the specific chemical constituents influencing this association remain unclear. In this study, we examined the association between PM constituents and oocyte quality in Hubei Province, China, using a generalized estimating equations model. We used a weighted quantile sum model to identify which PM constituents most strongly impact oocyte quality. Our results showed that exposure to PM constituents, including organic matter, black carbon, nitrate, sulfate, and ammonium, was associated with a decreased count of MII oocytes, 2PN oocytes, best cleavage-stage embryos, and increased rates of maturation failure and fertilization failure. Nitrate and organic matter demonstrated the strongest associations compared to the other constituents analysed. The most susceptible exposure windows differed depending on the reproductive outcomes measured, suggesting that different stages of follicular development exhibit differing sensitivities to PM exposures. These findings highlight the importance of reducing secondary aerosol precursor emissions, particularly those from fossil fuel combustion and biomass burning.
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3区Q1影响因子: 3.9
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22. Antioxidant-supplemented media modulates ROS by regulating complex I during mouse oocyte maturation.
期刊:Scientific reports
日期:2025-07-02
DOI :10.1038/s41598-025-08056-5
In Vitro Oocyte Maturation (IVM) is a technique used to mature oocytes in laboratory setting. However, IVM can lead to an imbalance of reactive oxygen species (ROS), which can damage the oocytes. To prevent this, antioxidants are added to the culture medium. How these antioxidants affect Complex I, a crucial ROS-producing protein within the mitochondrial membrane, remains uncertain. To address this gap, our study aimed to achieve two key objectives. First, we investigated, for the first time, the Complex I expression during mouse oogenesis. Second, we examined the influence of an antioxidant-containing medium on Complex I and ROS levels. Germinal vesicle (GV)-stage oocytes were incubated in culture media containing acetyl-l-carnitine (ALC), α-lipoic acid (ALA), MitoQ, N-acetyl-l-cysteine (NAC) until the metaphase I (MI) and metaphase II (MII) stages. Complex I and ROS levels increased in MI and MII oocytes. Additionally, ALA and NAC increased Complex I and ROS levels, while MitoQ decreased these levels in MI and MII oocytes. Interestingly, ALC did not affect MI oocytes, but decreased the Complex I and ROS levels in MII oocytes. By elucidating the interplay between antioxidants, Complex I, and ROS during oogenesis, we pave the way for future research to improve female fertility.
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2区Q1影响因子: 4.5
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23. Astaxanthin prevents postovulatory oocyte aging by targeting TNFR2 and inhibiting the TNF signaling pathway.
期刊:BMC biology
日期:2025-07-01
DOI :10.1186/s12915-025-02292-x
BACKGROUND:MII oocytes undergo time-dependent aging after ovulation, which is closely associated with impaired fertilization potential, poor embryo quality, and an increased risk of miscarriage. The apoptosis of cumulus cells and their secretion of TNF-α are identified as the primary contributors to postovulatory oocyte aging. RESULTS:In this study, we demonstrated that astaxanthin supplementation in culture medium effectively prevents postovulatory oocyte aging and extends oocyte lifespan in vitro. Importantly, this protective effect does not operate through the inhibition of cumulus cell apoptosis or TNF-α release. Notably, astaxanthin selectively binds to TNFR2 in oocytes, thereby preventing TNFR2 from interacting with TNF-α and inhibiting the activation of the TNF signaling pathway within oocytes. Furthermore, oocytes cultured with astaxanthin exhibit enhanced potential for early embryonic development and significantly increased IVF-ET litter size compared to controls. CONCLUSIONS:Our findings, based on a mouse model, provide valuable insights into the potential clinical application of astaxanthin in mitigating post-ovulatory oocyte aging.
Mercury, a prevalent heavy metal, negatively impacts oocyte maturation. However, the exact mechanism by which methylmercury chloride (MMC) affects this process remains elusive. The present study found that MMC administration triggered meiotic failure in oocytes by disrupting cumulus cell expansion, leading to compromised spindle apparatus and altered chromosomal architecture, which are crucial for oocyte development. This disruption is characterized by abnormal microtubule organization and defective chromosome alignment. Additionally, MMC exposure caused oxidative stress-induced apoptosis due to mitochondrial dysfunction, as indicated by decreased mitochondrial membrane potential, mitochondrial content, mitochondrial DNA copy number, and adenosine triphosphate levels. Proteomic analysis identified 97 differentially expressed proteins, including P62, an autophagy marker. Our results confirmed that MMC induced autophagy, particularly through the hyperactivation of the mitochondrial autophagy to remove damaged and normal mitochondria. The mitochondrial reactive oxygen species (ROS) scavenger Mito-TEMPO alleviated oxidative stress and mitochondrial autophagy levels, suggesting that mitochondrial ROS initiates this autophagic response. Notably, MMC activates mitochondrial autophagy via the monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signal pathway due to mitochondrial dysfunction. In vivo studies in mice revealed that MMC exposure decreased reproductive performance, attributed to excessive mitochondrial autophagy leading to reduced oocyte quality. Overall, these findings demonstrate that MMC exposure impairs oocyte maturation via the hyperactivation of mitochondrial autophagy induced by mitochondrial dysfunction.
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2区Q2影响因子: 2.5
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25. Microplastic exposure is associated with epigenomic effects in the model organism Pimephales promelas (fathead minnow).
期刊:The Journal of heredity
日期:2025-03-01
DOI :10.1093/jhered/esae027
Microplastics have evolutionary and ecological impacts across species, affecting organisms' development, reproduction, and behavior along with contributing to genotoxicity and stress. As plastic pollution is increasing and ubiquitous, gaining a better understanding of organismal responses to microplastics is necessary. Epigenetic processes such as DNA methylation are heritable forms of molecular regulation influenced by environmental conditions. Therefore, determining such epigenetic responses to microplastics will reveal potential chronic consequences of this environmental pollutant. We performed an experiment across two generations of fathead minnows (Pimephales promelas) to elucidate the transgenerational epigenetic effects of microplastic exposure. We exposed the first generation of fish to four different treatments of microplastics: two concentrations of each of pre-consumer polyethylene (PE) and PE collected from Lake Ontario. We then raised the first filial generation with no microplastic exposure. We used enzymatic methylation sequencing on adult liver tissue and homogenized larvae to evaluate DNA methylation differences among treatments, sexes, and generations. Our findings show the origin of the plastic had a larger effect in female minnows whereas the effect of concentration was stronger in the males. We also observed transgenerational effects, highlighting a mechanism in which parents can pass on the effects of microplastic exposure to their offspring. Many of the genes found within differentially methylated regions in our analyses are known to interact with estrogenic chemicals associated with plastic and are related to metabolism. This study highlights the persistent and potentially serious impacts of microplastic pollution on gene regulation in freshwater systems.
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2区Q1影响因子: 8.9
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26. PGC7 regulates maternal mRNA translation via AKT1-YBX1 interactions in mouse oocytes.
期刊:Cell communication and signaling : CCS
日期:2024-12-18
DOI :10.1186/s12964-024-01976-1
Timely and accurate translation of maternal mRNA is essential for oocyte maturation and early embryonic development. Previous studies have highlighted the importance of Primordial Germ cell 7 (PGC7) as a maternal factor in maintaining DNA methylation of maternally imprinted loci in zygotes. However, it is still unknown whether PGC7 is involved in the regulation of Maternal mRNA Translation. In this study, we have identified that PGC7-AKT1-YBX1 axis is involved in promoting the translation of maternal mRNAs. PGC7 not only sustains AKT1 activity by counteracting PP2A dephosphorylation and facilitating PDK1-AKT1 binding but also assists AKT1 in phosphorylating the translation inhibitor YBX1. In the absence of PGC7, despite increased PIK3CA expression and AKT1 phosphorylation, AKT1 is unable to phosphorylate YBX1. PGC7 facilitates the interaction between AKT1 and YBX1, enhancing YBX1-Serine 100 phosphorylation, which leads to YBX1 dissociation from eIF4E, thereby activating the translation of maternal Cyclin B1 and YAP1. The findings demonstrate the indispensability of PGC7 for translation activation in mammalian oocytes and provide a potential network regulated by PGC7 in early oogenesis.
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2区Q1影响因子: 3.7
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27. Nicotinic acid protects germinal vesicle oocyte meiosis against toxicity of benzo(a)pyrene in mice and humans.
期刊:Reproduction (Cambridge, England)
日期:2025-03-19
DOI :10.1530/REP-24-0364
In brief:Low concentrations of benzo(a)pyrene in the follicular fluid of smokers disrupt oocyte maturation, leading to meiotic defects. Nicotinic acid (NA) partially rescues these defects, offering insights into potential strategies for protecting fertility. Abstract:Benzo(a)pyrene (BaP), a carcinogen present in cigarette smoke, was detected in human follicular fluid at concentrations of approximately 5 nM in smokers and 7 nM in cases of assisted reproductive failure. However, whether a low concentration of BaP affects germinal vesicle (GV) oocyte maturation remains unclear. Here, we investigated the effects of 5 nM BaP on GV oocyte maturation in both mice and humans. In mice, GV oocytes were treated with 5 or 50 nM BaP, while human oocytes were exposed to 5 nM BaP. Our results demonstrated that 5 or 50 nM BaP exposure significantly inhibited first polar body extrusion during oocyte maturation. Mechanistic investigations revealed that BaP treatment downregulated Sirt1 protein expression in both GV and metaphase II (MII) stage mouse oocytes. Moreover, BaP exposure induced multiple cellular abnormalities, including spindle disorganization, cortical actin cap disruption, mitochondrial dysfunction and DNA damage in MII oocytes. Importantly, 15 μM NA supplementation increased Sirt1 expression and significantly rescued most of the abnormal effects. Subsequently, 5 nM BaP exposure impaired meiotic progression by reducing mitochondrial membrane potential and causing significant reactive oxygen species accumulation in human GV oocytes. Importantly, 15 μM NA supplementation partially rescued human GV oocytes from the toxicity of BaP during in vitro maturation (IVM). The present study indicated that a low BaP concentration in follicular fluid can significantly disrupt GV oocyte IVM, inducing meiotic defects in both mice and humans. NA has been shown to provide partial protection to GV oocyte meiosis against the toxicity of BaP during IVM.
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2区Q1影响因子: 2.7
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28. Impact of Flavonoid-Enriched Antioxidant Nanoformulation Supplementation on In Vitro Maturation and Gene Expression of Buffalo Oocytes.
期刊:Animals : an open access journal from MDPI
日期:2025-04-16
DOI :10.3390/ani15081147
Oocytes are exposed to various stressors during in vitro maturation (IVM). Antioxidant supplementation during IVM can mitigate oxidative stress. We investigated the effects of supplementing IVM medium with novel flavonoid-enriched antioxidant nanoformulations, namely, EMD-300 and EMP3-H200, on oocyte IVM and analyzed the expression of oxidative stress, apoptosis, and pluripotency genes in buffalo. Cumulus oocyte complexes (COCs) obtained from buffalo ovaries were matured in IVM medium supplemented with either EMD-300 or EMP3-H200 at 0.5% and 1.0% for 22 h. Following IVM, nuclear maturation, gene expression, and the levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) were analyzed. Nuclear maturation was lower ( < 0.001) for the 1.0% EMD-300 group than other groups. The expressions of the GPX4, SOD, CAT, and ATF6 genes were lower ( < 0.05) in the 0.5% EMD-300 and EMP3-H200 groups than in the control. OCT4 gene expression was higher ( < 0.05) for the treated groups than control group. The level of TAC in spent IVM medium was higher for the 0.5% EMD-300 and EMP3-H200 groups than for the control. However, the MDA concentrations were lower. In conclusion, supplementing IVM medium with EMD-300 or EMP3-H200 at 0.5% improved nuclear maturation of buffalo oocytes better than 1.0%. Our findings suggest that these compounds had antioxidant effects, which assures their ability in protecting oocytes against oxidative stress.
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2区Q1影响因子: 3.3
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29. Effects of CSTB on in vitro maturation of ovine oocytes.
期刊:Animal reproduction science
日期:2025-04-15
DOI :10.1016/j.anireprosci.2025.107839
Cystatin B (CSTB) primarily acts as an intracellular cysteine cathepsin inhibitor and plays important biological functions in multiple tissues. This study aimed to investigate the expression of CSTB in ovine ovaries and its effect on the in vitro maturation of ovine oocytes. We cloned a 390 bp CSTB cDNA fragment, containing 297 bp coding sequence and encoding 98 amino acids. The amino acid sequence of the homologues of ovine CSTB is 72.45-98.98 % similar to other species. In addition, CSTB is highly expressed in the ovary and uterus of the reproductive system, specifically localized in granulosa cells and oocytes. Adding recombinant CSTB to in vitro maturation medium increased the maturation rate, cleavage rate and blastocyst rate of small follicle oocytes. Conversely, interfering with CSTB knockdown reduced the maturation rate and developmental potential of oocytes. Recombinant protein upregulated mitochondrial membrane potential, ATP, and autophagy protein LC3A/LC3B in oocytes while downregulated reactive oxygen species. In contrast, CSTB knockdown reversed these trends, resulting in significant downregulation of membrane potential, ATP, and LC3A/LC3B and upregulation of reactive oxygen species. In conclusion, CSTB is a critical functional molecule for the in vitro maturation of ovine oocytes. It regulates oocyte developmental potential by modulating reactive oxygen species (ROS), membrane potential and autophagy in ovine oocytes. These findings enhance the understanding of the role of CSTB in ovine oocyte maturation in vitro.
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2区Q2影响因子: 3.5
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30. DNA methylation mechanisms in the maturing and ageing oocyte.
期刊:Epigenetics & chromatin
日期:2025-06-11
DOI :10.1186/s13072-025-00600-x
Oocyte maturation involves both nuclear and cytoplasmic processes that are critical for the acquisition of oocyte competence. Granulosa cells, surrounding the oocyte, play a pivotal role in the maturation process, with mechanisms such as cAMP signaling significantly influencing oocyte development. Epigenetic mechanisms - including DNA methylation and its oxidative derivatives, histone post-translational modifications and chromatin remodeling - interfere with the accessibility of transcription factors to regulatory regions of the genome, such as promoter regions of genes, hence generally regulating gene expression profiles; however, in oocytes, transcription is largely independent of DNA methylation patterns. Here we highlight epigenetic reprogramming events occurring during oocyte development and ageing, focusing on the establishment of gamete-specific epigenetic marks, including DNA modifications at imprinted regions, and age-related epigenetic changes. We focus on the mechanisms of DNA methylation and demethylation during mouse and human oocyte maturation, alongside an exploration of how ageing impacts the oocyte epigenome and its implications for reproductive success. By providing a comprehensive analysis of the role of epigenetics in oocyte development and maturation, this review addresses the importance of comprehending these processes to enhance in vitro fertilization treatments and improve reproductive outcomes.
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2区Q1影响因子: 7.3
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31. Ustiloxin A impairs oocyte quality by disrupting organelles function.
Oocyte quality is pivotal for fertilization and early embryonic development. Ustiloxin A (UA), is an emerging mycotoxin that has been frequently detected in rice and paddy. Because UA has been reported to be phytotoxic and cytotoxic, it poses a potential hazard to human and animal health. However, the effects of UA on oocyte maturation remain unknown. Here, we investigated the effects of acute UA exposure on mouse oocyte maturation. First, UA exposure inhibited oocyte maturation in a concentration-dependent manner and induced meiotic arrest by disrupting spindle assembly and reducing actin density. Moreover, mitochondrial function was substantially disrupted in oocytes upon UA exposure. Aberrant mitochondrial distribution, substantial downregulation of mitochondrial dynamics-associated genes Mfn1, Mfn2 and Fis1, decreased membrane potential and TOM20 expression were observed in UA-exposed oocytes; these effects further led to oxidative stress and DNA damage. Furthermore, UA induced ER and Golgi dysfunction and triggered ER stress by increasing GRP78 expression, which ultimately resulted in autophagy and early apoptosis in oocytes. Therefore, these results demonstrate that UA impairs oocyte quality by disrupting organelles function, providing new insight into the influence of UA on female reproduction in mammals.
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3区Q1影响因子: 3.3
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32. Melatonin improves the in vitro growth of bovine oocytes collected from early antral follicles by maintaining oocyte-cumulus cell communication.
期刊:Reproductive medicine and biology
日期:2025-01-28
DOI :10.1002/rmb2.12629
Purpose:In vitro, oocyte development is susceptible to oxidative stress, which leads to endoplasmic reticulum (ER) stress. This study investigated whether the antioxidant melatonin attenuates ER stress and maintains oocyte-cumulus cell communication during the in vitro growth (IVG) of bovine oocytes. Methods:Oocyte-granulosa cell complexes (OGCs) were harvested from slaughterhouse-derived ovaries and grown in vitro for 5 d at 38.5°C in 5% CO humidified air. Melatonin (10, 10, or 10 M) was added to the culture medium. Results:Oocyte diameter increased on day 5 from its initial value in all groups. The antrum formation rate was significantly higher in the 10 M melatonin-treated group than in the control. The melatonin-treated group showed reduced oxidative stress and increased gap junction communication compared with the control. ER stress-related genes in OGCs were significantly downregulated in the 10 M melatonin-treated group compared with those in the control. No significant changes were found in subsequent maturation among groups; however, 10 M melatonin treatment during IVG and IVM increased the maturation rate compared with that in the control. Conclusions:Melatonin reduces oxidative stress, which attenuates ER stress in OGCs during IVG of bovine oocytes and may improve IVG efficiency in assisted reproductive technology.
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1区Q1影响因子: 6.1
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33. Single-cell proteomics analysis of human oocytes during GV-to-MI transition.
期刊:Human reproduction (Oxford, England)
日期:2025-07-01
DOI :10.1093/humrep/deaf086
STUDY QUESTION:Which proteins are involved in the transition of human oocytes from the germinal vesicle (GV) to metaphase I (MI) phase? SUMMARY ANSWER:A total of 2369 proteins were identified, including 149 with significantly differential expression, 79 with upregulated expression in MI oocytes and 70 with downregulated expression. WHAT IS KNOWN ALREADY:During oocyte maturation, maternal proteins and RNA are stored to support early embryo development. However, GV oocytes matured in vitro have a lower chance of developing into blastocysts than MI oocytes. Therefore, identifying key differentially expressed proteins between the GV and MI stages can provide a better understanding of human oocyte development and maturation mechanisms and improve the utilization of oocytes. STUDY DESIGN, SIZE, DURATION:In total, 16 oocytes at the GV and MI stages were collected from female patients who underwent ovulation induction due to male factor infertility requiring embryo retrieval for ICSI. Differential proteins were identified in 16 oocytes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and the expression of several differential proteins was verified by immunofluorescence (IF). RNA interference was employed to identify the functions of specific proteins during oocyte maturation. PARTICIPANTS/MATERIALS, SETTING, METHODS:16 immature human oocytes discarded during ICSI cycles (eight GV oocytes and eight MI oocytes) were collected from 10 female patients. Two cohorts of oocytes underwent zona pellucida removal, lysis, and enzymatic digestion prior to peptide detection using LC-MS/MS methodology. Peptide detection outcomes were subjected to differential protein screening and functional annotation employing distinct analytical algorithms and datasets. To corroborate the sequencing findings, proteins exhibiting notable differential expression were authenticated via IF. Concerning protein functionality, siRNA was introduced during the GV phase, and oocyte maturation was evaluated through observation of polar body extrusion, alongside assessment of siRNA interference efficacy via IF analysis. MAIN RESULTS AND THE ROLE OF CHANCE:A total of 2369 proteins were identified, including 149 with significantly differential expression, 79 with upregulated expression in MI oocytes and 70 with downregulated expression. Gene ontology functional annotation and functional analysis revealed that these differentially expressed proteins are involved mainly in organic matter and cell metabolism, biological regulation, primary metabolism, nitrogen compound metabolism, and other biological processes. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes were involved mainly in the following pathways: transport and catabolism, signal transduction, protein folding, and energy and amino acid metabolism. The differentially expressed proteins included actin-related protein 2 (ACTR2), NADH: Ubiquinone Oxidoreductase Core Subunit S1 (NDUFS1), Tubulin Gamma Complex Component 3 (TUBGCP3), Heat Shock Protein Family B (Small) Member 1 (HSPB1), and Eukaryotic Translation Initiation Factor 3 Subunit B, which are involved mainly in mitochondrial function, cell division, and signal transduction. ACTR2, HSPB1, NDUFS1, and TUBGCP3 were selected for IF staining, and the difference in fluorescence intensity between GV and MI oocytes was consistent with the sequencing results. Three pairs of primers were designed for each gene corresponding to the top 10 differentially upregulated and downregulated proteins (with siRNAs successfully designed for eight upregulated and seven downregulated proteins) to study their function, and the results revealed that the protein expression of TUBGCP3 was downregulated after RNA interference. LARGE SCALE DATA:See supplementary tables. LIMITATIONS, REASONS FOR CAUTION:Although we have identified some differentially expressed proteins during the transition from human oocyte GV to MI stage, their crucial roles in oocyte maturation remain elusive. To elucidate the functions of these proteins in oocyte maturation, we have generated conditional knockout mice targeting selected proteins. WIDER IMPLICATIONS OF THE FINDINGS:We conducted single-cell level analysis to identify differentially expressed proteins between the human oocyte GV and MI stages. Our objective is to ascertain the potential of supplementing these proteins in the in vitro maturation culture medium to augment both oocyte maturation rates and quality. STUDY FUNDING/COMPETING INTEREST(S):This research was supported by the National Natural Science Foundation of China (82171599 and 82471657, B.X., 82301871, L.L.); China Postdoctoral Science Foundation (2024M763169, S.B.); and the National Key Research and Development Project of China (2029YFA0802600, B.X.). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER:N/A.
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4区Q2影响因子: 3.1
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34. Kaempferol attenuates cyclosporine-induced renal tubular injury via inhibiting the ROS-ASK1-MAPK pathway.
期刊:Naunyn-Schmiedeberg's archives of pharmacology
日期:2024-09-24
DOI :10.1007/s00210-024-03409-9
Cyclosporine (CSA) is a widely used immunosuppressive medication. CSA nephrotoxicity severely limits its application. Kaempferol (KPF), a naturally occurring phenolic compound, has a promising protective effect in reducing CSA-induced renal tubular injury, but the mechanism remains unknown. Our study aimed to determine the protective role of KPF against CSA-induced renal tubular injury. C57/B6 mice and the NRK-52E cell line were employed. CSA worsened renal function in mice, causing detachment and necrosis of tubular cells, leading to tubular vacuolation and renal interstitial fibrosis. CSA caused the detachment, rupture, and death of tubular cells in vitro, resulting in cell viability loss. KPF mitigated all these injurious alterations. KPF hindered CSA-induced ROS generation and protected renal tubular epithelial cells, similar to the antioxidant NAC. CSA lowered SOD activity and GSH levels while increasing MDA levels, and KPF ameliorated these changes. CSA caused phosphorylation of ASK1, JNK, and p38, similar to HO, whereas KPF significantly inhibited these changes. In conclusion, KPF reduces CSA-induced tubular epithelial cell injury via its antioxidant properties, inhibits the phosphorylation of ASK1, and inhibits the phosphorylation of p38 and JNK, implying that the synergistic use of KPF in CSA immunotherapy may be a promising option to reduce CSA-evoked renal injury.
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3区Q2影响因子: 3.5
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35. FSP1 regulates ferroptosis and mitochondrial function during mouse oocyte maturation.
期刊:Experimental cell research
日期:2025-03-18
DOI :10.1016/j.yexcr.2025.114524
Oocyte quality plays a fundamental role in fertilization and embryonic development. Emerging evidence indicates that ferroptosis may impair oocyte quality. Ferroptosis suppressor protein 1 (FSP1), a known ferroptosis inhibitor, has an uncharacterized function in regulating oocyte quality during meiotic maturation. This study identified FSP1 expression across all stages of meiotic maturation with localization to the cytoplasm of mouse oocytes. Aged mice exhibited a marked reduction in FSP1 expression within the ovaries and oocytes. Pharmacological inhibition of FSP1 disrupted germinal vesicle breakdown and polar body emission, leading to spindle defects and chromosome misalignment. Additionally, FSP1 inhibition persistently activated the spindle assembly checkpoint, resulting in meiotic arrest. At the mechanistic level, inhibition of FSP1 led to an increase in intracellular Fe levels, enhanced dihydroethidium fluorescence, excessive accumulation of reactive oxygen species, and intensified lipid peroxidation. Disruptions in ferroptosis-associated gene expression further indicated that oocytes underwent ferroptosis. Moreover, mitochondrial dysfunction was evident following FSP1 inhibition, as reflected by aberrant mitochondrial distribution, diminished ATP production, and an elevated mitochondrial membrane potential. Collectively, these results establish FSP1 as a key regulator of oocyte meiotic maturation by modulating iron homeostasis and mitochondrial function, while its inhibition triggers ferroptosis-dependent meiotic failure.
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1区Q1影响因子: 9.4
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36. ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development.
期刊:Genome biology
日期:2025-05-08
DOI :10.1186/s13059-025-03593-8
BACKGROUND:During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins that are important for the regulation of maternal mRNA stability. RESULTS:Smart-seq2 analysis reveals drastically downregulated maternal transcripts. However, the detection of transcript levels by Smart-seq2 may be biased by the polyadenylated tail length of the mRNAs. Similarly, differential expression of maternal transcripts in oocytes with or without Zar1/2 differs when analyzed using total RNA-seq and Smart-seq2, suggesting an influence of polyadenylation. Combined analyses using total RNA-seq, LACE-seq, PAIso-seq2, and immunoprecipitation-mass spectrometry reveals that ZAR1 may target the 3'-untranslated regions of maternal transcripts, regulates their stability in germinal vesicle stage oocytes, and interacts with other proteins to control the polyadenylation of mRNAs. CONCLUSIONS:The jointly analyzed multi-omics data highlight the limitations of Smart-seq2 in oocytes, clarify the dynamics of the maternal transcriptome, and uncover new roles of ZAR1 in regulating the maternal transcriptome.
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2区Q1影响因子: 4.2
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37. Bioflavonoid luteolin prevents sFlt-1 release via HIF-1α inhibition in cultured human placenta.
期刊:FASEB journal : official publication of the Federation of American Societies for Experimental Biology
日期:2023-08-01
DOI :10.1096/fj.202300611R
Preeclampsia (PE) is a serious hypertensive complication of pregnancy and is a leading cause of maternal death and major contributor to maternal and perinatal morbidity, including establishment of long-term complications. The continued prevalence of PE stresses the need for identification of novel treatments which can target prohypertensive factors implicated in the disease pathophysiology, such as soluble fms-like tyrosine kinase 1 (sFlt-1). We set out to identify novel compounds to reduce placental sFlt-1 and determine whether this occurs via hypoxia-inducible factor (HIF)-1α inhibition. We utilized a commercially available library of natural compounds to assess their ability to reduce sFlt-1 release from primary human placental cytotrophoblast cells (CTBs). Human placental explants from normotensive (NT) and preeclamptic (PE) pregnancies were treated with varying concentrations of luteolin. Protein and mRNA expression of sFlt-1 and upstream mediators were evaluated using ELISA, western blot, and real-time PCR. Of the natural compounds examined, luteolin showed the most potent inhibition of sFlt-1 release, with >95% reduction compared to vehicle-treated. Luteolin significantly inhibited sFlt-1 in cultured placental explants compared to vehicle-treated in a dose- and time-dependent manner. Additionally, significant decreases in HIF-1α expression were observed in luteolin-treated explants, suggesting a mechanism for sFlt-1 downregulation. The ability of luteolin to inhibit HIF-1α may be mediated through the Akt pathway, as inhibitors to Akt and its upstream regulator phosphatidylinositol-3 kinase (PI3K) resulted in significant HIF-1α reduction. Luteolin reduces anti-angiogenic sFlt-1 through inhibition of HIF-1α, making it a novel candidate for the treatment of PE.
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2区Q1影响因子: 4.7
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38. Inhibitory effect of diacerein on diclofenac-induced acute nephrotoxicity in rats via modulating SIRT1/HIF-1α/NF-κB and SIRT1/p53 regulatory axes.
期刊:International immunopharmacology
日期:2024-03-12
DOI :10.1016/j.intimp.2024.111776
The aim of this study is to explore the potential of repurposing the antiarthritic drug diacerein (DCN) against diclofenac (DCF)-induced acute nephrotoxicity in rats. Rats were divided into four groups: Group I (CTRL) served as the negative control; Group II (DCF) served as the positive control and was injected with DCF (50 mg/kg/day) for three consecutive days (fourth-sixth) while being deprived of water starting on day 5; Group III (DCF + DCN50) and Group IV (DCF + DCN100) were orally administered DCN (50 and 100 mg/kg/day, respectively) for six days and injected with DCF, while being deprived of water as described above. Changes in kidney function biomarkers were assessed. Levels of MDA and GSH along with NO content in kidney tissues were measured as indicators of oxidative stress status. Histopathological changes of the renal cortex and medulla were evaluated. Changes in renal NF-κB and SIRT-1 levels were immunohistochemically addressed. Western blotting was used to estimate the relative expressions of HIF-1α, p53, and active caspase-3. Our results showed that DCN inhibited kidney dysfunction and suppressed oxidative stress, which were reflected in improved kidney architecture, including less tubular degeneration and necrosis in the cortex and medulla. Interestingly, DCN reduced renal HIF-1α, p53, and active caspase-3 expression and NF-κB activation while increasing renal SIRT1 expression. In conclusion, for the first time, DCN counteracts acute kidney injury induced by DCF in rats by its anti-oxidative, anti-inflammatory, antinecrotic, and anti-apoptotic effects in a dose-dependent manner, which are mainly via targeting SIRT1/HIF-1α/NF-κB and SIRT1/p53 regulatory axes.
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2区Q1影响因子: 2.5
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39. Supplementation with lipoamide during in vitro maturation improves bovine oocyte maturation and subsequent embryonic development: potential link to PI3K/AKT signaling.
期刊:Theriogenology
日期:2025-05-03
DOI :10.1016/j.theriogenology.2025.117417
Oxidative stress during oocyte in vitro maturation (IVM) is still concerned. Lipoamide (LAM) has been widely studied as an agent for alleviating various diseases associated with oxidative disruption. This work aimed to evaluate the potential effects of LAM on bovine oocyte IVM and its mechanisms. Different concentrations of LAM (0, 10, 50, 100, and 200 μmol/L) were supplemented to bovine oocyte IVM medium. The IVF derived zygote cleavage and blastocyst formation rate in the 100 μmol/L LAM treatment group was increased compared with the control group (P < 0.05).There was no statistical difference in PBI between 100 μmol/L LAM treatment and the control group, although the treatment tended to increase it (P = 0.059). Further revealed that LAM increased the expression of PI3K and phosphorylated-AKT1 (pAKT1), improved mitochondrial profile, and reduced apoptosis in bovine oocytes. Meanwhile, the reactive oxygen species (ROS) as well as the 8-Hydroxydeoxyguanosine (8-OHdG, DNA damage-specific marker) displayed lower levels accumulation in LAM-exposed oocytes. Taken together, the results show that administration of LAM (100 μmol/L) during IVM can ameliorate the developmental competence of bovine oocyte through the potential regulation of oxidative stress, apoptosis, DNA damage, and PI3K/AKT signaling.
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2区Q2影响因子: 3.7
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40. Transcriptional insights on the incomplete cytoplasmic maturation and developmental potential of oocytes cultured without granulosa cells in mice.
期刊:BMC genomics
日期:2025-03-18
DOI :10.1186/s12864-025-11455-7
BACKGROUND:Oocyte maturation is crucial for female fertility and embryonic development, encompassing nuclear and cytoplasmic maturation. Supportive cells of follicles, such as granulosa cells, are essential for oocyte growth and maturation. Oocytes can achieve nuclear maturation without granulosa cells during in vitro maturation (IVM). However, there is still a higher chance of incomplete cytoplasmic maturation for these oocytes with mature nuclei compared with oocytes cultured with granulosa cells. Oocytes with incomplete cytoplasmic maturation have lower fertilization rates and developmental potential than mature ones, although underlying mechanisms are poorly understood. Identifying key genes and signaling pathways associated with oocyte cytoplasmic maturation can help further elucidate the maturing process of oocytes and understand the impact of immature oocytes on embryonic development, throwing insights into the strategy to improve the success rate of assisted reproductive technologies. RESULTS:Our study investigated murine oocytes maturing with and without granulosa cells. IVM without granulosa cells yielded oocytes with lower nuclear maturation rates than IVM with granulosa cells and in vivo maturation (IVO). Even though oocytes could achieve nuclear maturation without granulosa cells, they showed incomplete cytoplasmic maturation featuring higher levels of reactive oxygen species, lower mitochondrial density, and higher proportions of cells with abnormal distributions of cortical granules. Of note, oocytes with immature and mature cytoplasm had distinct transcriptional profiles. In the immature oocytes, we observed a deficient mRNA restoration of genes in crucial regulatory pathways of cellular growth and division, potentially affecting embryonic development. Differentially expressed genes (DEGs) between immature and mature oocytes were identified to be highly expressed in different pre-implantation stages, such as the MII oocyte, the 8-cell stage, and the ICM stage. Identified DEGs were enriched in key regulatory pathways of fertilization and embryonic development, such as energy and metabolic pathways. These observations indicated that the impeded development potential of oocytes with immature cytoplasm might be the result of abnormal gene expressions during oocyte maturation. CONCLUSIONS:We show that granulosa cells are important for both nuclear and cytoplasmic maturation of oocytes. Abnormal gene expression in oocytes with incomplete cytoplasmic maturation may be associated with potential defects in fertilization and embryonic development.
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3区Q2影响因子: 4
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41. Kaempferol promotes angiogenesis through HIF-1α/VEGF-A/Notch1 pathway in ischemic stroke rats.
期刊:Neurochemistry international
日期:2025-02-21
DOI :10.1016/j.neuint.2025.105953
Stroke is a severe disease characterized by the obstruction of blood vessels in the central nervous system. An essential therapeutic strategy for ischemic stroke is strengthening angiogenesis, which effectively promotes the long-term recovery of neurological function. Therefore, it is critical to explore and develop new drugs that promote angiogenesis after ischemic stroke. Kaempferol has been employed to treat ischemic diseases; However, its proangiogenic effects in ischemic stroke remain unclear. In the study, we explored the long-term therapeutic effects and mechanisms of kaempferol on ischemic stroke in vivo and in vitro. A rat model of autologous thrombus stroke and oxygen-glucose deprivation (OGD)-induced human brain microvascular endothelial cells (HBMECs) model was established to assess the effects of kaempferol in vivo (50 mg/kg/d, ig, 14 d) and in vitro (0.1, 0.3, 1 μmol L). The results showed that long-term administration of kaempferol ameliorated neurological deficits and infarct volume in ischemic stroke rats. In addition, kaempferol relieved vascular embolization; enhanced microvascular endothelial cell survival, proliferation, migration, and lumen formation; increased the density of microvessels in the peri-infarct cortex; and promoted neovascular structure remodeling by increasing the coverage of astrocyte end-feet and expression of tight-junction proteins (TJPs). Further analysis revealed that the HIF-1α/VEGF-A/Notch1 signaling pathway was activated by kaempferol, and that inhibition of Notch1 blocked kaempferol-induced angiogenesis. Taken together, our results indicate that kaempferol exerts neuroprotective effects by stimulating endogenous angiogenesis and neovascular structural remodeling via the HIF-1α/VEGF-A/Notch1 signaling pathway, suggesting the therapeutic potential of kaempferol in ischemic stroke.
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1区Q1影响因子: 8.3
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42. Forsythoside A mitigates osteoarthritis and inhibits chondrocyte senescence by promoting mitophagy and suppressing NLRP3 inflammasome via the Nrf2 pathway.
期刊:Phytomedicine : international journal of phytotherapy and phytopharmacology
日期:2024-10-02
DOI :10.1016/j.phymed.2024.156052
BACKGROUND:Chondrocyte senescence and inflammation are hallmarks of osteoarthritis (OA). Forsythiaside A (FTA), a phenylethanol glycoside isolated from air-dried fruits of Forsythia, has been reported to have significant anti-inflammatory and antioxidant properties. However, its protective effects against OA have not been elucidated. PURPOSE:We explored the therapeutic efficacy of FTA in inhibiting chondrocyte senescence and inflammation during OA, as well as the potential underlying mechanisms. STUDY DESIGN:This study aimed to investigate the novel mechanism of FTA in alleviating OA in both cell and animal models. METHODS:The protective effect of FTA against tert‑butyl hydroperoxide-induced chondrocyte damage was assessed, and the effects of FTA on cartilage aging and OA progression were evaluated using a medial meniscus (DMM)-induced knee OA mouse model. The regulatory effects of FTA on the NLRP3 Inflammasome, mitophagy, and the PKC/Nrf2 pathway were also explored. RESULTS:In vitro, FTA improved mitochondrial function, enhanced mitophagy, suppressed NLRP3 inflammasome activation, and inhibited chondrocyte senescence; however, these chondroprotective effects were partially reversed after mitophagy inhibition, NLRP3 inflammasome activation, and Nrf2 pathway inhibition. Furthermore, we found that FTA directly interacts with Nrf2 and enhances its phosphorylation by protein kinase C (PKC). In vivo, FTA attenuated the pathological signs of knee OA in a DMM-model mouse model, which was partially reversed by ML385. CONCLUSION:FTA inhibited chondrocyte senescence and OA progression by activating the PKC-Nrf2 pathway. Thus, FTA is a potential novel therapeutic agent for OA.
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2区Q1影响因子: 4.7
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43. Forsythiaside A alleviates myocardial injury in streptozotocin-induced diabetes via endoplasmic reticulum stress-NLRP3 inflammasome pathway.
期刊:International immunopharmacology
日期:2024-12-31
DOI :10.1016/j.intimp.2024.113956
The aim of this study was to evaluate for the effects of forsythiaside A (FA) on myocardial injury in streptozotocin (STZ)-induced diabetes mice. Blood glucose (BG), serum triglycerides (TG), lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), cardiac troponin (cTnI), malondialdehyde (MDA), superoxide dismutase (SOD) levels were detected in STZ mice. The structure and function of heart was observed via cardiac ultrasound. Cytokine levels in mouse serum and heart were detected using enzyme-linked immunosorbent assay (ELISA) as well as TG, LDH, CK-MB, cTnI, MDA and SOD in high glucose (Glu) induced H9c2 cells. Western blot detection of the expression of endoplasmic reticulum stress-related TXNIP/NLRP3 inflammasome pathways (GRP78, PERK, P-PERK, EIF-α, P-EIF-α, XBP1, ATF6, TXNIP and NLRP3) in SCD mice and LCG induced H9c2 cells. Endoplasmic reticulum stress activator tunicamycin (TM) was used to validate the above pathway for FA. It was also found that FA had protective effects on myocardial injury in STZ mice via restored heart function, improved cardiac pathological changes and suppressed inflammatory response as well as in Glu induced H9c2 cells. In conclusion, FA alleviated myocardial injury in diabetes via endoplasmic reticulum stress-NLRP3 inflammasome pathway.
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3区Q1影响因子: 3.5
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44. Extracellular vesicles secreted by cumulus cells contain microRNAs that are potential regulatory factors of mouse oocyte developmental competence.
期刊:Molecular human reproduction
日期:2024-05-30
DOI :10.1093/molehr/gaae019
The role of cumulus cells (CCs) in the acquisition of oocyte developmental competence is not yet fully understood. In a previous study, we matured cumulus-denuded fully-grown mouse oocytes to metaphase II (MII) on a feeder layer of CCs (FL-CCs) isolated from developmentally competent (FL-SN-CCs) or incompetent (FL-NSN-CCs) SN (surrounded nucleolus) or NSN (not surrounding nucleolus) oocytes, respectively. We observed that oocytes cultured on the former could develop into blastocysts, while those matured on the latter arrested at the 2-cell stage. To investigate the CC factors contributing to oocyte developmental competence, here we focused on the CCs' release into the medium of extracellular vesicles (EVs) and on their miRNA content. We found that, during the 15-h transition to MII, both FL-SN-CCs and FL-NSN-CCs release EVs that can be detected, by confocal microscopy, inside the zona pellucida (ZP) or the ooplasm. The majority of EVs are <200 nm in size, which is compatible with their ability to cross the ZP. Next-generation sequencing of the miRNome of FL-SN-CC versus FL-NSN-CC EVs highlighted 74 differentially expressed miRNAs, with 43 up- and 31 down-regulated. Although most of these miRNAs do not have known roles in the ovary, in silico functional analysis showed that seven of these miRNAs regulate 71 target genes with specific roles in meiosis resumption (N = 24), follicle growth (N = 23), fertilization (N = 1), and the acquisition of oocyte developmental competence (N = 23). Overall, our results indicate CC EVs as emerging candidates of the CC-to-oocyte communication axis and uncover a group of miRNAs as potential regulatory factors.
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4区Q4影响因子: 2.2
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45. Nephroprotective effect of Ginsenoside Rg1 in lipopolysaccharide-induced sepsis in mice through the SIRT1/NF-κB signaling.
期刊:Folia histochemica et cytobiologica
日期:2024-04-02
DOI :10.5603/fhc.97140
INTRODUCTION:During sepsis, the kidney is one of the most vulnerable organs. Sepsis-associated acute kidney injury (S-AKI) is hallmarked by renal inflammation, apoptosis, and oxidative injury. Ginsenoside Rg1 (Rg1) is a natural product that possesses abundant pharmacological actions and protects against many sepsis-related diseases. Nevertheless, its role and related mechanism in S-AKI remain to be determined. MATERIALS AND METHODS:S-AKI was induced using lipopolysaccharide (LPS, 10 mg/kg) via a single intraperitoneal injection. Rg1 (200 mg/kg) was intraperitoneally administered for 3 consecutive days before LPS treatment. For histopathological examination, murine kidney tissues were stained with hematoxylin and eosin. Tubular injury score was calculated to evaluate kidney injury. Serum creatinine and BUN levels were measured for assessing renal dysfunction. The levels and activities of oxidative stress markers (MDA, 4-HNE, PC, GSH, SOD, and CAT) in renal tissue were measured by corresponding kits. Renal cell apoptosis was detected by TUNEL staining. The protein levels of apoptosis-related markers (Bcl-2, Bax, and Cleaved caspase-3), proinflammatory factors, SIRT1, IκBα, p-NF-κB p65, and NF-κB p65 in kidneys were determined using western blotting. Immunofluorescence staining was employed to assess p-NF-κB p65 expression in renal tissues. RESULTS:LPS-induced injury of kidneys and renal dysfunction in mice were ameliorated by Rg1. Rg1 also impeded LPS-evoked renal cell apoptosis in kidneys. Moreover, Rg1 attenuated LPS-triggered inflammation and oxidative stress in kidneys by inhibiting proinflammatory cytokine release, enhancing antioxidant levels and activities, and reducing lipid peroxidation. However, all these protective effects of Rg1 in LPS-induced AKI mice were reversed by EX527, an inhibitor of sirtuin 1 (SIRT1). Mechanistically, Rg1 upregulated SIRT1 protein expression, increased SIRT1 activity, and inactivated NF-κB signaling in the kidney of LPS-induced AKI mice, which was also reversed by EX527. CONCLUSIONS:Rg1 ameliorates LPS-induced kidney injury and suppresses renal inflammation, apoptosis, and oxidative stress in mice via regulating the SIRT1/NF-κB signaling.
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3区Q1影响因子: 4.7
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46. Resveratrol attenuates cyclosporin A-induced upregulation of the thromboxane A receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in the rat mesenteric artery.
期刊:European journal of pharmacology
日期:2024-04-04
DOI :10.1016/j.ejphar.2024.176543
Cyclosporin A, an immunosuppressive agent, is extensively utilized for the prevention of transplant rejection and treat autoimmune disease in the clinic, despite its association with a high risk of hypertension development among patients. Resveratrol is a kind of non-flavonoid phenolic compound that widely exists in many plants. The aim of the present study was to investigate the mechanism by which resveratrol ameliorates cyclosporin A-induced hypertension. The arterial rings of the mesentery were incubated with cyclosporin A and resveratrol in vitro. Rats were administered cyclosporin A and/or resveratrol for 3 weeks in vivo. Blood pressure was measured via the tail arteries. Vasoconstriction curves were recorded using a sensitive myograph. The protein expression was evaluated through Western blotting. This study demonstrated that resveratrol mitigated the cyclosporin A-induced increase in blood pressure in rats. Furthermore, resveratrol markedly inhibited the cyclosporin A-induced upregulation of thromboxane A receptor-mediated vasoconstriction in the rat mesenteric artery both in vitro and in vivo. Moreover, resveratrol activated AMPK/SIRT1 and inhibited the MAPK/NF-κB signaling pathway. In conclusion, resveratrol restored the cyclosporin A-induced upregulation of the thromboxane A receptor and hypertension via the AMPK/SIRT1 and MAPK/NF-κB pathways in rats.
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3区Q2影响因子: 2.5
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47. d-galactose causes embryonic development arrest and placental development disorders in mice by increasing ROS and inhibiting SIRT1/FOXO3a axis.
期刊:Placenta
日期:2024-04-06
DOI :10.1016/j.placenta.2024.04.003
INTRODUCTION:Does an elevation in d-Galactose (D-Gal) levels within the body contribute to abnormal embryonic development and placental dysfunction during pregnancy? METHODS:Mouse embryos were cultivated to the blastocyst stage under varying concentrations of D-Gal. The blastocyst formation rate was measured, and the levels of reactive oxygen species (ROS), sirtuin 1 (SIRT1), and forkhead box O3a (FOXO3a) in blastocysts were assessed. Mice were intraperitoneally injected with either saline or D-Gal with or without SRT1720. On the 14th day of pregnancy, the fetal absorption rate and placental weight were recorded. Placental levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. The expression of senescence-related factors, such as senescence-associated β-galactosidase (SA-β-gal) in the placenta was examined, and the expression of placental SIRT1, FOXO3a and p21 was evaluated by immunohistochemistry and Western blotting. RESULTS:D-Gal adversely affects early embryonic development in vitro, resulting in a decreased blastocyst formation rate. Furthermore, D-Gal downregulates SIRT1 and FOXO3a while increasing ROS levels in blastocysts. Concurrently, D-Gal induces placental dysfunction, characterized by an elevated fetal absorption rate, reduced placental weight, diminished SOD activity, and increased MDA content. The senescence-related factor SA-β-gal was detected in the placenta, along with altered expression of placental SIRT1, FOXO3a, and p21. The SIRT1 agonist SRT1720 mitigated this damage by increasing SIRT1 and FOXO3a expression. DISCUSSION:The inhibition of early embryonic development and placental dysfunction induced by D-Gal may be attributed to the dysregulation of SIRT1. Activating SIRT1 emerges as a potentially effective strategy for alleviating the adverse effects of D-Gal exposure.
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3区Q1影响因子: 3.4
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48. Kaempferol promotes flap survival by inhibiting ferroptosis and inflammation through network pharmacology and in vivo experiments.
期刊:Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
日期:2025 Jan-Feb
DOI :10.1111/wrr.13250
Skin flap transplantation is a primary method for wound repair; however, postoperative skin flap necrosis remains a significant challenge. Kaempferol, a flavonol abundant in various foods, exhibits diverse pharmacological effects. This study investigated the potential targets of kaempferol for treating skin flap ischemia-reperfusion (I/R) injury through network pharmacology and molecular docking, followed by in vivo validation. Using SwissTargetPredict, PubChem, SymMap V2, and GeneCards databases, 174 potential target proteins of kaempferol were identified. KEGG and GO enrichment analyses, performed using R software, indicated that kaempferol promotes skin flap survival by modulating ferroptosis, TNF-α, and NF-κB signalling pathways. Molecular docking demonstrated stable binding between kaempferol and key proteins, including SIRT1 and NRF2. In vivo, a McFarlane skin flap model was established in Sprague-Dawley rats. Kaempferol treatment improved flap survival, enhanced perfusion areas and distal arteriole visualisation, and increased blood flow in the flap. Furthermore, kaempferol reduced neutrophil infiltration, alleviated oxidative stress, improved mitochondrial morphology and function, and inhibited the release of proinflammatory cytokines. Western blot and immunofluorescence analyses confirmed that kaempferol inhibited ferroptosis and inflammation while promoting flap survival. Mechanistically, kaempferol was found to activate SIRT1-mediated HMGB1/TLR4/NF-κB and NRF2/SLC7A11/GPX4 pathways, thereby promoting skin flap survival and mitigating I/R injury.
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4区Q3影响因子: 1.7
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49. Forsythiaside A Ameliorates Inflammation by Regulating the Autophagy in Methotrexate-induced Intestinal Mucositis.
期刊:Combinatorial chemistry & high throughput screening
日期:2025-01-29
DOI :10.2174/0113862073324564241211064620
BACKGROUND:Methotrexate (MTX) effectively eliminates cancerous cells but can also cause inflammation intestinal, known as mucositis. Forsythiaside A (FTA) from Forsythia suspensa has shown promise in relieving mucositis by targeting the NLRP3 pathways. Since NLRP3 inflammasome activation is negatively regulated by autophagy, this study explores how FTAmediated autophagy affects NLRP3 inflammasome in treating MTX-induced intestinal inflammation. METHODS:Intestinal mucositis was induced in rats with MTX. FTA's impact was assessed using HE staining and ELISA. The mechanism was studied using immunofluorescence, western blot, and ELISA. RESULTS:FTA treatment resulted in reduced levels of D-lactic acid and diamine oxidase (DAO) in MTX-treated rats. Western blot and immunofluorescence analyses revealed up-regulation of Beclin- 1 and LC3II/I, accumulation of LC3, and down-regulation of p62 expression levels in MTXtreated rats following 40 or 80 mg/kg FTA intervention. However, when the autophagy inhibitor 3-MA was used, the intestinal pathology was exacerbated, the inflammatory scores increased, and serum levels of TNF-α, IL-1β, and IL-18 were elevated. Western blotting indicated decreased LC3II/I expression, while NLRP3, cleaved caspase 1, and cleaved IL-1β expressions were upregulated. CONCLUSION:These findings suggested that FTA alleviated MTX-treated intestinal mucositis by activating autophagy, which in turn inhibits the NLRP3 inflammasome.
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4区Q2影响因子: 2.8
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50. Exposure of Porcine Oocytes to Methylparaben During In Vitro Maturation Alters the Expression of Genes Involved in Cumulus Cell Expansion and Steroidogenesis, Decreasing Hyaluronic Acid and Progesterone Synthesis.
期刊:Journal of applied toxicology : JAT
日期:2024-11-26
DOI :10.1002/jat.4727
Parabens are widely used because of their antimicrobial properties in drugs, cosmetics, and food; however, it has been reported that methylparaben may adversely influence female reproduction. Methylparaben decreases oocyte in vitro maturation at a maturation inhibition concentration 50 of 780.31 μM but also decreases oocyte viability at a lethal concentration 50 of 2028.38 μM. Additionally, parabens are endocrine disruptors, affecting steroidogenesis as well as cumulus cell expansion. Therefore, the aim of this study was to elucidate some of the mechanisms by which methylparaben alters cumulus cell expansion and decreases oocyte maturation through the evaluation of gene expression related to cumulus cell expansion, hyaluronic acid, and progesterone synthesis. For this, oocytes were exposed to different methylparaben concentrations of 0 (control), 650, 780, and 1000 μM for 20 and 44 h of in vitro maturation. The cumulus cell expansion rates, maturation rates, gene expression rates, and hyaluronic acid and progesterone concentrations were revaluated after 20 and 44 h of culture. At sublethal concentrations, methylparaben decreased in vitro maturation as well as cumulus cell expansion at 44 h. Additionally, methylparaben decreased the expression of Has2 and Cd44 at 20 and 44 h of maturation. The expression levels of Stard1, Cyp11a1, and Hsd3b1 were also altered by methylparaben exposure at 20 and 44 h of maturation, suggesting its role as an endocrine disruptor. Hyaluronic acid and progesterone concentrations in the culture medium decreased at 20 and 44 h. These findings could partially explain some of the mechanisms by which methylparaben alters female fertility.
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2区Q1影响因子: 2.5
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51. Mangiferin promotes porcine oocyte maturation and delays the postovulatory aging process by up-regulating NRF2 levels.
期刊:Theriogenology
日期:2025-03-10
DOI :10.1016/j.theriogenology.2025.117384
Mangiferin (MGN), a flavonoid known for its anti-inflammatory and antioxidant properties, was evaluated in this study for its effects on porcine oocyte maturation in vitro, as well as its potential to modulate the mechanisms associated with aging oocytes. The inclusion of 0.1 μM MGN in the IVM culture medium significantly enhanced blastocyst development following parthenogenetic activation, while also notably upregulating the expression of key embryonic development genes, including SOX2, PCNA, POU5F1, and DNMT3A. MGN treatment improved the oocytes' antioxidant capacity and mitochondrial functionality, concurrently reducing cathepsin B activity and lowering LC3B protein expression (1.06 ± 0.09 vs. 0.55 ± 0.12). To investigate the underlying mechanisms, NRF2 expression was assessed, revealing a marked increase in NRF2 fluorescence and a significant elevation in both NRF2 mRNA and protein levels (1.00 ± 0.05 vs. 1.25 ± 0.09) following MGN treatment compared to the control group. Additionally, MGN treatment enhanced the early developmental potential of aged oocytes, elevating GSH levels and mitochondrial membrane potential and reducing ROS accumulation. Furthermore, MGN treatment upregulated antioxidant genes (SOD1, SOD2). Collectively, these findings suggest that MGN improves porcine oocyte maturation in vitro and enhances subsequent developmental potential through the activation of NRF2 signaling. Moreover, MGN may also delay postovulatory oocyte aging by boosting antioxidant defense and mitochondrial function in aged oocytes.
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4区Q2影响因子: 3.3
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52. Quercetin alleviates hyperoxia-induced bronchopulmonary dysplasia by inhibiting ferroptosis through the MAPK/PTGS2 pathway: Insights from network pharmacology, molecular docking, and experimental evaluations.
期刊:Chemical biology & drug design
日期:2024-04-01
DOI :10.1111/cbdd.14520
Quercetin, a bioactive natural compound renowned for its potent anti-inflammatory, antioxidant, and antiviral properties, has exhibited therapeutic potential in various diseases. Given that bronchopulmonary dysplasia (BPD) development is closely linked to inflammation and oxidative stress, and quercetin, a robust antioxidant known to activate NRF2 and influence the ferroptosis pathway, offers promise for a wide range of age groups. Nonetheless, the specific role of quercetin in BPD remains largely unexplored. This study aims to uncover the target role of quercetin in BPD through a combination of network pharmacology, molecular docking, computer analyses, and experimental evaluations.
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3区Q2影响因子: 1.7
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53. Thiamethoxam Exposure Impairs Oocyte Maturation via Induction of Lipid Metabolism and Mitochondrial Dysfunctions in Porcine.
期刊:Reproduction in domestic animals = Zuchthygiene
日期:2025-03-01
DOI :10.1111/rda.70020
Neonicotinoid insecticides (NEOs) are the most widely used pesticides in modern agriculture, and there are residues in the environment and food. Thiamethoxam (TMX) has been proven to destroy the ovarian homeostasis of mice in vivo and reduce the development of porcine oocytes in vitro. However, whether TMX can interfere with porcine oocyte maturation and its potential mechanism remains unknown. This study indicated that TMX affects the expansion of cumulus cells, destroys the balance of lipid metabolism, and damages mitochondrial function. TMX treatment decreased the expression of genes related to cumulus cell expansion, lipid synthesis and mitochondrial synthesis. Collectively, results confirm that TMX exposure can damage oocyte maturation and produce reproductive toxicity by inducing lipid metabolism and mitochondrial dysfunction in porcine.
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2区Q1影响因子: 2.7
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54. Coenzyme Q10 Supplementation Effects on In Vitro Oocyte Maturation, Lipid Peroxidation, and Embryonic Development in Prepubertal and Aging Thai-Holstein Cows.
期刊:Animals : an open access journal from MDPI
日期:2024-12-25
DOI :10.3390/ani15010018
This study investigated the effects of coenzyme Q10 (CoQ10) supplementation on in vitro oocyte maturation, lipid peroxidation, and embryonic development in prepubertal and aging Thai-Holstein cows. First, we used slaughterhouse-derived oocytes to confirm that CoQ10 (50 μM) significantly enhanced cleavage (53.33% vs. 37.50%) and blastocyst formation rates (46.81% vs. 27.50%). Thereafter, oocytes were collected from four prepubertal and four aging cows via ovum pick-up and matured in vitro with or without CoQ10 supplementation. The follicular development and oocyte quality were assessed. Aging cows exhibited significantly more follicles (24.00 vs. 16.67) and greater oocyte recovery (16.67 vs. 11.67) than prepubertal cows. Additionally, CoQ10 supplementation significantly reduced malondialdehyde levels in aging cows (1.28 vs. 0.61 nmol/mL), indicating reduced lipid peroxidation. Finally, CoQ10 significantly improved cleavage rates in both age groups (prepubertal: 22.50 to 32.50%; aging: 41.71 to 65.00%) and blastocyst formation rates in aging cows (prepubertal: 17.50 to 20.00%; aging: 31.44 to 53.72%). These results suggest that CoQ10 supplementation enhances oocyte maturation and embryonic development, particularly in aging cows, likely by mitigating oxidative stress and supporting mitochondrial function. Therefore, CoQ10 may be a valuable supplement in assisted reproductive technologies for improving reproductive efficiency in cattle breeding programs.
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3区Q1影响因子: 4.9
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55. Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes.
期刊:International journal of molecular sciences
日期:2024-12-06
DOI :10.3390/ijms252313144
The efficacy of assisted reproductive technologies (ARTs) in older women remains constrained, largely due to an incomplete understanding of the underlying pathophysiology. This review aims to consolidate the current knowledge on age-associated mitochondrial alterations and their implications for ovarian aging, with an emphasis on the causes of mitochondrial DNA (mtDNA) mutations, their repair mechanisms, and future therapeutic directions. Relevant articles published up to 30 September 2024 were identified through a systematic search of electronic databases. The free radical theory proposes that reactive oxygen species (ROS) inflict damage on mtDNA and impair mitochondrial function essential for ATP generation in oocytes. Oocytes face prolonged pressure to repair mtDNA mutations, persisting for up to five decades. MtDNA exhibits limited capacity for double-strand break repair, heavily depending on poly ADP-ribose polymerase 1 (PARP1)-mediated repair of single-strand breaks. This process depletes nicotinamide adenine dinucleotide (NAD⁺) and ATP, creating a detrimental cycle where continued mtDNA repair further compromises oocyte functionality. Interventions that interrupt this destructive cycle may offer preventive benefits. In conclusion, the cumulative burden of mtDNA mutations and repair demands can lead to ATP depletion and elevate the risk of aneuploidy, ultimately contributing to ART failure in older women.
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2区Q1影响因子: 2.5
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56. Effect of BMP15 and GDF9 in the IVM medium on subsequent oocyte competence and embryo development of prepubertal goats.
期刊:Theriogenology
日期:2024-12-18
DOI :10.1016/j.theriogenology.2024.12.015
Oocyte-secreted factors (OSFs), such as BMP15 and GDF9, are soluble paracrine factors that drive cumulus cell differentiation and function, sustaining oocyte competence acquisition and embryo development. This study aimed to assess the effect of BMP15 and GDF9 on IVM medium of prepubertal goat oocytes. COCs were in vitro matured in absence (control group) or presence of 100 ng/mL of BMP15, GDF9, or both. To determine cumulus-oocyte communication, transzonal projections (TZP) density at 0h, 6h, 12h and 24h of IVM were evaluated. After IVM, mitochondrial activity, intracellular ROS and glutathione (GSH) levels, the epidermal growth factor receptor (EGFR) expression in oocytes and cumulus cells, and cumulus expansion were assessed. Blastocyst production and quality were evaluated after parthenogenetic activation (PA) and IVF. IVM supplementation with BMP15 increased the TZP density during the first 6 h of culture. After IVM, BMP15 increased mitochondrial activity, EGFR expression in oocytes and cumulus cells, and cumulus expansion compared to control, but ROS and GSH levels were similar to control. BMP15 improved blastocyst production following PA (15.5 % vs 6.3 %) and the number of cells in the blastocyst inner cell mass. No differences were observed on blastocyst production or quality following IVF. IVM supplementation with GDF9 did not improve results from control group in any parameters studied. Additionally, GDF9 in combination with BMP15 only improved mitochondrial activity and cumulus expansion over control. In conclusion, IVM medium supplementation with BMP15 (100 ng/ml) improves COCs quality parameters and PA-blastocyst production and quality of prepubertal goat oocytes. However, GDF9 (100 ng/mL) did not have any beneficial effect in this study and was possibly antagonistic to BMP15.
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2区Q1影响因子: 3.7
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57. Beneficial effects of melatonin on canine oocyte nuclear maturation via reduction of oxidative stress.
期刊:Reproduction (Cambridge, England)
日期:2025-03-14
DOI :10.1530/REP-24-0388
In brief:Oxidative stress due to high-fat content damages canine oocytes during long period of in vitro maturation and compromises their developmental competence. This paper shows how melatonin protects the oocytes and increases development to metaphase II stage. Results from this study would be applicable to conservation of endangered and other animal species. Abstract:Unlike other domesticated animals, in vitro maturation of canine oocytes results in poor nuclear maturation to the metaphase II stage and high oocyte degeneration. The high-fat content of canine oocytes is the likely cause; it predisposes them to oxidative stress and deleterious reactive oxygen species (ROS). Melatonin (MTN) (potentially acting as a powerful antioxidant) was reported to support in vitro cultured oocytes in other species. In this work, canine cumulus oocyte complexes (COCs) were collected after routine ovariohysterectomy. Immunocytochemistry for expression of melatonin receptors (MTNR-1A and 1B) revealed that both receptors were highly expressed in canine oocytes and there was lower expression in the cumulus cells. Canine COCs matured in vitro in melatonin-supplemented culture at 100 nM concentration in low (5%) O2 incubator had a lower percentage at GV stage (6.7% ± 4.2 vs 19.8% ± 3), a higher MII stage (32.3% ± 6.4 vs 15.81% ± 8.1), lower degeneration (20.5% ± 3.2 vs 45.2% ± 5.15) and higher meiotic resumption (GVBD-MII; 56.2% ± 8.6 vs 19% ± 3), and produced lower ROS (determined after DCHFDA staining) (all P < 0.005) than oocytes cultured in high O2 (20%) incubator. The expression of ROS-regulating genes GPX-1 and catalase was significantly reduced in oocytes cultured with melatonin in low O2 compared with high O2 (P < 0.05). Importantly, the oocyte maturation rate increased significantly when G-IVF PLUS, a commercial culture medium used in human oocyte culture, was supplemented with MTN (P < 0.05). These results support the main objective of this study to analyze the beneficial effects of melatonin and low oxygen tension on both health and the developmental competence of in vitro matured canine oocytes.
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3区Q2影响因子: 1.7
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58. 6-Gingerol and Astaxanthin Mitigate the Effects of Stearic Acid in Pig Oocyte Maturation.
期刊:Reproduction in domestic animals = Zuchthygiene
日期:2024-11-01
DOI :10.1111/rda.14746
Elevated non-esterified fatty acids (NEFAs), particularly stearic acid (SA), have a deleterious effect on oocyte maturation, leading to developmental damage and reproductive issues. High SA levels disrupt metabolic processes, inducing lipotoxicity that impairs oocyte quality and contributes to reproductive failures through early embryonic losses. This research investigates the lipotoxic effects of SA and assesses the protective potential of 6-Gingerol (6-G) and Astaxanthin (AX) on porcine oocytes during in vitro maturation (IVM). Herein, 6100 cumulus-oocyte complexes (COCs) were exposed to various concentrations of SA (25-250 μM) to elucidate the concentration-dependent effect on oocyte viability, polar body extrusion (PBE) and cumulus cell expansion index (CCEI). However, the efficacy of 6-G (5-15 μM) and AX (2.5 μM) in combination with SA at 150 μM (SA6) concentration was evaluated to mitigate these adverse effects. The results indicated that SA6 substantially reduced oocyte viability, PBE and CCEI, demonstrating its toxic impact on oocyte developmental competence (p < 0.0001). Moreover, treatment with antioxidants such as SA6 + 6-G (10 μM) and SA6 + AX showed a considerable increase in viability and PBE compared to SA6 alone (p < 0.05). These findings demonstrate the importance of lipid metabolism in oocyte health, where dysregulation impairs reproductive capacity. Both 6-G and AX protected against lipotoxicity induced by SA6 while enhancing lipid homeostasis and the anti-oxidative defences necessary for maintaining cellular integrity. This study finds substantial evidence that optimising the microenvironment with specific antioxidants can improve oocyte quality and provide invaluable knowledge in reproductive technologies and fertility treatments.
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2区Q1影响因子: 3.3
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59. Atractylenolide Ⅲ partially alleviates tunicamycin-induced damage in porcine oocytes during in vitro maturation by reducing oxidative stress.
期刊:Animal reproduction science
日期:2024-12-29
DOI :10.1016/j.anireprosci.2024.107761
Assisted reproductive technology (ART) is widely used to address infertility and enhance reproductive outcomes in livestock. Among various ART techniques, in vitro maturation (IVM) is commonly used to obtain high-quality oocytes but is susceptible to oxidative stress. In traditional Chinese medicine, Rhizoma Atractylodis Macrocephalae (Bai Zhu) is used to enhance maternal and fetal health. Atractylenolide Ⅲ (AⅢ), a major component of Bai Zhu, has shown both antioxidant properties and oxidative stress induction, leading to controversy. This study used porcine oocytes as a model to investigate the effects of AⅢ under tunicamycin (TM)-induced oxidative stress. During IVM, oocytes were treated with various concentrations of AⅢ and a constant dose of TM. AⅢ promoted oocyte maturation and cumulus cell expansion, with the optimal concentration being 1 mg/L. AⅢ reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, indicating reduced oxidative damage. Mitochondrial function and membrane potential (MMP) were preserved in AⅢ-treated oocytes. Additionally, AIII could alleviate TM-induced endoplasmic reticulum (ER) stress, as shown by decreased mRNA expression of ER stress markers. Following parthenogenetic activation (PA), AⅢ-treated oocytes exhibited increased cleavage and blastocyst formation rates with reduced apoptosis compared to the TM group. These findings suggest that AⅢ protects against oxidative stress, improving oocyte quality and developmental potential, with potential applications in ART.
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3区Q3影响因子: 1.2
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60. Curcumin Suppresses ROS Production and Increases Mitochondrial Activity in Cumulus Cells and Oocytes of COCs Derived From Non-Vascularized Follicles in Pigs.
In vitro maturation (IVM) produces offspring from domestic animals; however, the blastocyst rate after IVM was low. We previously reported that the developmental competence of oocytes derived from follicles with blood vessels absent on the surface (non-vascularized follicles: NVF) is quite low compared to those derived from follicles with blood vessels present on the surface (vascularized follicles: VF). Thus, it is important to develop technique to improve the quality of NVF-derived oocyte by IVM. Since it has been reported that reactive oxygen species (ROS) reduces oocyte quality, in this study, we investigated whether curcumin that is known as antioxidant could improve oocyte quality derived from NVF. As results, cultivation of NVF Cumulus-oocyte complexes (COCs) with curcumin significantly improved cumulus expansion and oocyte meiotic maturation of NVF COCs compared to those of NVF COCs without curcumin. Cultivation with curcumin of NVF COCs significantly improved the proliferative activity of cumulus cells. Furthermore, the cultivation significantly reduced ROS activity and increased mitochondrial activity. Hence, it was revealed that the addition of curcumin to the maturation medium increased mitochondrial activity and reduced ROS levels in NVF-derived cumulus cells and oocytes, thereby improving the maturation of oocytes within COCs.
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2区Q1影响因子: 2.5
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61. Supplementation with N-Acetyl-L-cysteine during in vitro maturation improves goat oocyte developmental competence by regulating oxidative stress.
期刊:Theriogenology
日期:2025-01-17
DOI :10.1016/j.theriogenology.2025.01.016
Oocyte quality can affect mammal fertilization rate, early embryonic development, pregnancy maintenance, and fetal development. Oxidative stress induced by reactive oxygen species (ROS) is one of the most important causes of poor oocyte maturation in vitro. To reduce the degree of cellular damage caused by ROS, supplementation with the antioxidant N-Acetyl-L-cysteine (NAC) serves as an effective pathway to alleviate glutathione (GSH) depletion during oxidative stress. This study investigated the effects of NAC supplementation during in vitro maturation of goat oocytes and explored the molecular mechanisms of maturation by transcriptome sequencing of MⅡ oocytes. The results showed that 1.5 mM NAC significantly increased the rates of oocyte maturation and cumulus cell expansion and improved the subsequent development of embryos. During the subsequent culture of parthenogenetically activated embryos, 1.5 mM NAC significantly increased the division rate of oocytes and blastocyst rate. It also reduced the accumulation of ROS, increased the level of GSH, alleviated oxidative stress, and enhanced the antioxidant capacity and cell metabolic activity. Transcriptome sequencing results revealed that NAC treatment significantly increased the expression of SIRT1, GGCT, and MITF genes related to the cellular antioxidant system, as well as the IDH3G gene related to energy metabolism, and decreased the expression of CASP8, FOS, and MMP1 genes related to apoptosis and cell invasion, as well as the CCL2. and CXCL8 genes related to the inflammatory response. In conclusion, the findings suggest that NAC supplementation significantly reduces oxidative stress, improves antioxidant capacity and metabolic activity, promotes oocyte maturation, and improves oocyte quality.
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2区Q1影响因子: 4.3
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62. Epigenetic Cross-Talk Between Sirt1 and Dnmt1 Promotes Axonal Regeneration After Spinal Cord Injury in Zebrafish.
期刊:Molecular neurobiology
日期:2024-08-07
DOI :10.1007/s12035-024-04408-w
Though spinal cord injury (SCI) causes irreversible sensory and motor impairments in human, adult zebrafish retain the potent regenerative capacity by injury-induced proliferation of central nervous system (CNS)-resident progenitor cells to develop new functional neurons at the lesion site. The hallmark of SCI in zebrafish lies in a series of changes in the epigenetic landscape, specifically DNA methylation and histone modifications. Decoding the post-SCI epigenetic modifications is therefore critical for the development of therapeutic remedies that boost SCI recovery process. Here, we have studied on Sirtuin1 (Sirt1), a non-classical histone deacetylase that potentially plays a critical role in neural progenitor cells (NPC) proliferation and axonal regrowth following SCI in zebrafish. We investigated the role of Sirt1 in NPC proliferation and axonal regrowth in response to injury in the regenerating spinal cord and found that Sirt1 is involved in the induction of NPC proliferation along with glial bridging during spinal cord regeneration. We also demonstrate that Sirt1 plays a pivotal role in regulating the HIPPO pathway through deacetylation-mediated inactivation of Dnmt1 and subsequent hypomethylation of yap1 promoter, leading to the induction of ctgfa expression, which drives the NPC proliferation and axonal regrowth to complete the regenerative process. In conclusion, our study reveals a novel cross-talk between two important epigenetic effectors, Sirt1 and Dnmt1, in the context of spinal cord regeneration, establishing a previously undisclosed relation between Sirt1 and Yap1 which provides a deeper understanding of the underlying mechanisms governing injury-induced NPC proliferation and axonal regrowth. Therefore, we have identified Sirt1 as a novel, major epigenetic regulator of spinal cord regeneration by modulating the HIPPO pathway in zebrafish.
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2区Q2影响因子: 3
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63. Follicular-fluid extracellular vesicles support energy metabolism of bovine oocytes, improving blastocyst development and quality†.
期刊:Biology of reproduction
日期:2025-07-13
DOI :10.1093/biolre/ioaf096
Extracellular vesicles (EVs) from follicular fluid (FF) seem to play a significant role in communication within ovarian follicles in several species. The present study aimed to examine the supporting effect of FF-derived small EVs (FF-sEVs) during in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs) under conditions of disturbed energy metabolism. Bovine COCs were matured in vitro with inhibitors targeting lipid metabolism (etomoxir) or glucose metabolism (iodoacetate combined with dehydroepiandrosterone), in the presence or absence of FF-sEVs. Following maturation, oocytes and cumulus cells were analyzed by real-time quantitative polymerase chain reaction (qPCR) and stained to visualize lipid droplets. The uptake of FF-sEVs was visualized by fluorescent labeling. In vitro fertilization and embryo culture were followed by mass spectrometry analysis of hatched blastocysts. We demonstrate for the first time that FF-sEVs are transported from the medium into the oocytes, via the cumulus cells and through transzonal projections into the perivitelline space and ooplasm. Cumulus cells under metabolic stress conditions exhibit an increased FF-sEV uptake from the maturation medium. FF-sEV supplementation during metabolic stress conditions enhances the MII rate in oocytes and positively affects subsequent embryo development and quality revealed by altered metabolic activity. Lipid droplet parameters and gene expression in cumulus cells and oocytes are affected by FF-sEV supplementation, which is more pronounced in cumulus cells. Our findings show that FF-sEV supplementation during IVM under metabolic stress conditions significantly affects COCs, with a positive effect on further blastocyst quality. We provide novel insights into the role of FF-sEVs in oocyte maturation and blastocyst development.
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3区Q1影响因子: 2.3
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64. Tauroursodeoxycholic Acid Enhances the Quality of Postovulatory Aged Oocytes by Alleviating Oxidative Stress, Apoptosis, and Endoplasmic Reticulum Stress in Pigs.
期刊:Veterinary sciences
日期:2025-03-12
DOI :10.3390/vetsci12030265
One of the major factors causing reduced developmental capacity of aged porcine oocytes is the induction of oxidative stress during oocyte aging. Tauroursodeoxycholic acid (TUDCA) supports cellular function by acting as an antioxidant and free radical scavenger. The aim of this study is to evaluate whether exogenous supplementation of TUDCA to the porcine in vitro maturation system can ameliorate the compromised quality of aged oocytes by mitigating free radical production. We found that TUDCA was able to effectively maintain normal oocyte morphology, cortical granule distribution, and spindle structure during postovulatory aging. Additionally, the blastocyst rate and total cell number in blastocysts were significantly increased in aged porcine oocytes treated with TUDCA. Importantly, aged porcine oocytes treated with TUDCA reduced ROS levels, increased the expression levels of GSH and genes, and improved the mitochondrial membrane potential ratio. Further study demonstrated that TUDCA significantly alleviated apoptosis in aged porcine oocytes, confirmed by the decreased Caspase 3 levels and ratio of to . Interestingly, TUDCA could effectively alleviate the phenomenon of endoplasmic reticulum stress triggered during the oocyte aging process. Taking these findings together, our study demonstrates that TUDCA supplementation beneficially affects the quality of aged porcine oocytes by suppressing oxidative stress, apoptosis, and endoplasmic reticulum stress.
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2区Q1影响因子: 2.5
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65. Equol promotes the in vitro maturation of porcine oocytes by activating the NRF2/KEAP1 signaling pathway.
期刊:Theriogenology
日期:2024-11-22
DOI :10.1016/j.theriogenology.2024.11.015
In vitro maturation (IVM) plays a critical role in embryo production. However, the quality of IVM oocytes often suffers from oxidative stress due to the excessive accumulation of ROS. Equol, a metabolite of soybean flavonoids, exhibits potent antioxidant activity. This study investigated the effects of equol on porcine oocyte IVM. Our findings showed that treatment with 5 μM equol significantly enhanced cumulus cell expansion and the first polar body extrusion in porcine oocytes. Moreover, equol also improved the subsequent embryonic development capacity of the oocytes after parthenogenetic activation. Additionally, equol improved mitochondrial function by increasing mitochondrial content, membrane potential, and ATP levels, while promoting lipid droplet accumulation in oocytes. Equol also reduced DNA damage and early apoptosis, with an associated upregulation of BCL2 and downregulation of BAX expression. Notably, equol decreased ROS levels, likely through activation of the NRF2/KEAP1 antioxidant pathway, leading to increased expression of HO-1, CAT, GPX1, and SOD. In conclusion, equol improves porcine oocyte IVM by mitigating oxidative stress via activation of the NRF2/KEAP1 pathway, offering a potential strategy for optimizing the IVM system in porcine oocytes.
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2区Q1影响因子: 2.5
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66. Beta-aminoisobutyric acid improves bovine oocyte maturation and subsequent embryonic development by promoting lipid catabolism.
期刊:Theriogenology
日期:2024-12-18
DOI :10.1016/j.theriogenology.2024.12.016
Energy metabolism homeostasis is essential for oocyte maturation and acquisition of developmental capacity. However, bovine oocyte in vitro maturation (IVM) is highly susceptible to metabolic stress and lipid accumulation. β-Aminoisobutyric acid (BAIBA), a metabolite produced in response to skeletal muscle exercise, has been reported to be involved in lipid and glucose metabolism, as well as inflammation and oxidative stress. This work aimed to evaluate the potential effects of BAIBA on bovine oocyte IVM and its mechanisms. Different concentrations of BAIBA (10, 20, 50, 100, and 200 μmol/L) were supplemented to bovine oocyte IVM medium. Results shown the BAIBA (50 μmol/L) had no effect on the extrusion rate of the first polar body of oocytes but significantly improved the subsequent blastocyst formation rate and embryo quality. Further revealed that supplementing BAIBA significantly up-regulated expression levels of genes to fatty acid β-oxidation metabolism (CPT1A, CPT1B and CPT2), promoted lipid metabolism, lowered lipid content, and improved mitochondrial membrane potential and active mitochondria content. Importantly, BAIBA stimulation significantly increased the phosphorylation of AMP-activated protein kinase (AMPK); and the inhibition of AMPK activity (Compound C, AMPK inhibitor) suppressed the ability of BAIBA to promote lipid metabolism in oocytes. Besides, inhibition of AMPK lowered the oocyte maturation rate and the subsequent zygote cleavage and blastocyst formation rate when compared to that of the BAIBA treatment. The results indicated that BAIBA was mainly involved in promoting lipid catabolism by activation of AMPK, consequently enhancing oocyte development potential.
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3区Q1影响因子: 4.9
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67. In Vitro Toxicity of a DEHP and Cadmium Mixture on Sheep Cumulus-Oocyte Complexes.
期刊:International journal of molecular sciences
日期:2024-12-24
DOI :10.3390/ijms26010005
Di-(2-ethylhexyl) phthalate (DEHP) and Cadmium (Cd) affect female reproduction. To date, toxicological research has focused on the effects of individual contaminants, whereas living beings are exposed to mixtures. This study analyzed the effects of a DEHP/Cd mixture on nuclear and cytoplasmic maturation of sheep cumulus-oocyte complexes (COCs) compared with single compounds. COCs recovered from slaughterhouses-derived sheep ovaries were in vitro exposed to 0.5 μM DEHP, 0.1 μM Cd, or DEHP/Cd mixture at the same concentrations during 24 h of in vitro maturation (IVM). After IVM, oocyte nuclear chromatin configuration was evaluated, and bioenergetic/oxidative parameters were assessed on expanded cumulus cells (CCs) and matured oocytes (chi-square test and one-way ANOVA; < 0.05). Under examined conditions, oocyte nuclear maturation was never impaired. However, COC bioenergetics was affected with stronger effects for the mixture than single compounds. Indeed, the percentages of matured oocytes with healthy mitochondrial distribution patterns were reduced ( < 0.001 and < 0.05 for mixture and single compounds, respectively). Oocyte mitochondrial membrane potential, intracellular ROS levels, and mitochondria/ROS co-localization were reduced, with the same significance level, in all contaminated conditions. CCs displayed increased ROS levels only upon mixture exposure ( < 0.001). In conclusion, in vitro exposure to the DEHP/Cd mixture affected COC quality in the sheep to a greater extent than separate compounds.
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2区Q1影响因子: 2.5
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68. Editing the growth differentiation factor 9 gene affects porcine oocytes in vitro maturation by inactivating the maturation promoting factor.
期刊:Theriogenology
日期:2025-02-07
DOI :10.1016/j.theriogenology.2025.02.004
Growth differentiation factor 9 (GDF9), an oocyte-secreted factor, plays a vital role in porcine oocyte development. However, its function during oocyte in vitro maturation (IVM) remains unclear. In this study, we achieved GDF9 editing in approximately 59 % of cultured oocytes by cytoplasmic injection of a pre-assembled crRNA-tracrRNA-Cas9 ribonucleoprotein complex into porcine oocytes at the germinal vesicle (GV) stage. GDF9 editing caused significant damage to porcine oocytes during IVM. Additionally, GDF9 editing impaired mitochondrial function, increased reactive oxygen species (ROS) accumulation, and decreased glutathione (GSH) levels. The impaired IVM of GDF9-edited porcine oocytes was primarily driven by active cAMP-PKA signaling, which inhibited MOS expression, leading to the activation of the WEE1B/MYT1 kinase and inactivation of CDC25B phosphatase. This cascade resulted in the inactivation of CDK1, thereby preventing the activation of maturation-promoting factor (MPF) and inhibiting first polar body (PB1) extrusion. Our findings enhance the understanding of GDF9's regulatory role in porcine oocyte IVM and provide a theoretical foundation for improving porcine reproductive performance.
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2区Q1影响因子: 2.5
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69. Effect of human chorionic gonadotropin on oocyte maturation and developmental competence in buffalo.
期刊:Theriogenology
日期:2024-12-30
DOI :10.1016/j.theriogenology.2024.12.029
We hypothesized that human chorionic gonadotropic (hCG) could replace LH in the maturation media for buffalo oocytes, and hCG administration before ovum pick-up (OPU) enhances in-vitro development of buffalo oocytes. Objectives were 1) to investigate the effect of hCG supplementation on nuclear maturation, oocyte development, and granulosa cell mRNA abundance of genes related to growth and antioxidant pathways and 2) to determine the effect of hCG administration before OPU on in-vitro oocyte development. In Experiment 1, buffalo oocytes retrieved from slaughterhouse ovaries were maturated in the media supplemented with 0.5 μg of LH or 2 IU of hCG. After fertilization, cleavage and embryo were assessed on 48 h and 7 d of the culture, respectively. The nuclear maturation of the oocytes and granulosa cells mRNA abundance of genes (AREG,EREG,NRG1,CYP19A1,GDF9,CASP9,SOD1) were assessed after maturation. In Experiment 2, buffaloes were synchronized and superstimulated with FSH and 6 h before OPU, randomly assigned to either receive saline (CON, n = 4) or 1500 IU of hCG (hCG, n = 6). Four OPU sessions per buffalo were conducted at weekly intervals and retrieved oocytes were maturated and fertilized in-vitro. In Experiment 1, nuclear maturation, cleavage, embryo production, and mRNA abundance of the genes related to growth and steroidogenesis did not differ between treatments but SOD1 gene expression tended (P = 0.10) to lower in hCG treatment as compared with LH. In Experiment 2, oocytes retrieved from hCG-treated buffaloes resulted in a higher proportion of cleavage (84.0 vs. 42.5 ± 8.9 %, P = 0.02) and embryo (84.0 vs 24.0 ± 7.3, P < 0.01) than CON. In conclusion, hCG supplementation in the maturation media yielded comparable outcomes to that of LH, and hCG administration 6 h before OPU enhanced the in-vitro developmental competency of the buffalo oocytes.
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4区Q2影响因子: 3.5
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70. Quercetin attenuates the symptoms of osteoarthritis and by suppressing ferroptosis via activation of AMPK/Nrf2/Gpx4 signaling.
期刊:Molecular medicine reports
日期:2024-12-24
DOI :10.3892/mmr.2024.13425
Osteoarthritis (OA) is a common joint disorder involving the cartilage and other joint tissues. Quercetin (QCT) serves a protective role in the development of OA. However, to the best of our knowledge, the regulatory mechanisms of QCT in the progression of OA have not yet been fully elucidated. In order to mimic a model of OA , IL‑1β was used to stimulate chondrocytes. Furthermore, an animal model of OA was induced by anterior cruciate ligament transection (ACLT). 5‑Ethynyl‑2'‑deoxyuridine assays, TUNEL assays, ELISAs, western blotting and immunohistochemical assays were conducted to assess the chondroprotective properties of QCT in the development of OA. The results revealed that 100 µM QCT significantly promoted the proliferation, reduced the apoptosis and inflammation, and inhibited the extracellular matrix (ECM) degradation in IL‑1β‑stimulated chondrocytes. Additionally, QCT attenuated the IL‑1β‑induced ferroptosis of chondrocytes, as demonstrated by the reduced lipid reactive oxygen species and Fe levels. Conversely, the inhibitory effects of QCT on the apoptosis and inflammatory responses were reversed by the activation of ferroptosis by erastin in IL‑1β‑stimulated chondrocytes. Furthermore, QCT significantly elevated the level of phosphorylated (p‑)5' AMP‑activated protein kinase (AMPK) and the levels of two negative regulators of ferroptosis [nuclear factor erythroid 2‑related factor 2 (Nrf2) and glutathione peroxidase 4 (Gpx4)] in IL‑1β‑stimulated chondrocytes. The AMPK inhibitor compound C notably reversed the promoting effects of QCT on phosphorylated‑AMPK, Nrf2 and Gpx4 expression in IL‑1β‑stimulated chondrocytes. Additionally, QCT markedly ameliorated the destruction and degradation of articular cartilage, and elevated the p‑AMPK, Nrf2 and Gpx4 levels in the mouse model of ACLT‑induced OA. Overall, the present study demonstrated that QCT inhibited the development of OA by suppressing ferroptosis via the activation of the AMPK/Nrf2/Gpx4 signaling pathway. These findings provide novel insights into the regulatory mechanisms of QCT for the treatment of patients with OA.
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2区Q2影响因子: 3
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71. Suppression of oocyte glycine transporter activity in mouse cumulus-oocyte complexes before resumption of meiosis†.
期刊:Biology of reproduction
日期:2025-07-13
DOI :10.1093/biolre/ioaf080
Glycine is a key regulator of cell volume in early preimplantation mouse embryos and supports embryo viability. Its accumulation is initiated when the GLYT1 glycine transporter (SLC6A9) is activated in oocytes at about the same time the oocyte is released from meiotic arrest at the germinal vesicle (GV) stage. The mechanism by which GLYT1 is maintained in an inactive state before ovulation is triggered is unknown. Here, we have shown that GLYT1 activity can remain suppressed in isolated cumulus-oocyte complexes (COCs) under defined culture conditions that include keeping COCs physically separated and using the physiological mediator of GV arrest, natriuretic peptide precursor C. When GV arrest is instead maintained in oocytes within COCs by inhibiting phosphodiesterase 3A or cyclin-dependent kinase 1, GLYT1 similarly remains inactive. However, GLYT1 becomes activated in isolated GV oocytes similarly maintained in GV arrest, indicating that cumulus cells are required for suppressing GLYT1 activity. This implies that meiotic arrest is necessary but not sufficient for preventing GLYT1 activation and that an inhibitory factor likely arising from the cumulus is also required. Finally, we have found that pyrrophenone, a selective inhibitor of arachidonic acid production by cytoplasmic phospholipase A alpha, causes GLYT1 to become activated in oocytes within COCs despite maintenance of meiotic arrest of the oocyte. Since arachidonic acid levels decrease in oocytes after release from GV arrest, we propose that arachidonic acid may be a candidate for the inhibitory factor in COCs that regulates GLYT1 activity.
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2区Q1影响因子: 8
英汉
72. DEHP regulates ferritinophagy to promote testicular ferroptosis via suppressing SIRT1/PGC-1α pathway.
期刊:The Science of the total environment
日期:2024-09-24
DOI :10.1016/j.scitotenv.2024.176497
To increase elasticity and flexibility, di-2-ethylhexyl phthalate (DEHP) is used in a variety of industrial products, but excessive exposure to it can pose a threat to human health. In epidemiological studies of population exposure to DEHP, attention has been paid to damage to the male reproductive system. However, the toxicological mechanism of DEHP regarding testicular injury is not well understood. We used Western blot analysis, transmission electron microscopy, fluorescence staining, transient transfection and assay kit to detect relevant indicators, and the results were as follows: After DEHP exposure, the expression levels of ACSL4, COX2, TF, FTH1, LC3, AMPK, p-AMPK, ULK1, p-ULK1, serum iron, tissue iron and MDA in the exposure group were significantly increased. The expression levels of GPX4, NCOA4, p62, SIRT1, and PGC-1α, as well as the contents of GSH and ATP, decreased. Electron microscopy showed that more autophagosomes were observed. Our findings suggest that exposure to DEHP induced ferritinophagy and ferroptosis in the testis. In vitro, the promoting effect of ferritinophagy on ferroptosis was verified by applying the autophagy inhibitor (3-MA) and si-NCOA4. Moreover, Mono-(2-ethylhexyl) phthalate (MEHP) inhibited the mitochondrial regulatory protein SIRT1/PGC-1α, leading to mitochondrial dysfunction. Changes in mitochondrial reactive oxygen species (MtROS) and energy over-activated AMPK/ULK1 autophagy pathway, and then promoted ferritinophagy, which increased the sensitivity of TM4 cells to ferroptosis. This research offers a theoretical framework for the prevention and management of DEHP-induced harm.
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2区Q1影响因子: 7.3
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73. PFOS exposure impairs porcine oocyte maturation and embryo development via mitochondria-dependent ferroptosis.
Perfluorooctane sulfonate (PFOS) is a widely utilized chemical known for its exceptional environmental stability over extended periods, its significant potential to bioaccumulate in living organisms, and its considerable risks to both health and the environment. Several studies have suggested that PFOS may pose reproductive risks in mammals; however, the exact mechanisms driving these effects are not well understood. In this study, we explored the possible mechanisms by which PFOS toxicity affects the maturation of mammalian oocytes and the embryonic development employing porcine oocytes as a model system. SMART-seq results suggested that PFOS may affect oocyte maturation through mechanisms involving ferroptosis, autophagy, and alterations in membrane structure. Our results suggest that PFOS exposure adversely affects mitochondrial function and structure, thereby influencing peroxisome biogenesis and contributing to oxidative stress. Most importantly, we found that exposure to PFOS significantly elevated Fe levels, an indicator associated with ferroptosis in oocytes. Furthermore, malondialdehyde (MDA) levels in the PFOS group were significantly higher than those in the control group. Additionally, the mRNA expression levels of PCBP1 and PCBP2, which are related to ferroptosis, as well as the expression level of P53, were significantly reduced in the PFOS group. Overall, exposure to PFOS in vitro results in mitochondrial damage in porcine oocytes, which induces lipid peroxidation and subsequently leads to the occurrence of ferroptosis.
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4区Q2影响因子: 3.2
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74. Activation of SIRT3/AMPK/mTOR-mediated autophagy promotes quercetin-induced ferroptosis in oral squamous cell carcinoma.
期刊:Human & experimental toxicology
日期:2025 Jan-Dec
DOI :10.1177/09603271251323753
INTRODUCTION:Quercetin has been reported to inhibit the growth of oral squamous cell carcinoma (OSCC), but the mechanism remains unclear. Therefore, our study aimed to investigate the involvement of sirtuin 3 (SIRT3) and the autophagy-dependent form of cell death, ferroptosis, in the pathogenesis of OSCC, and observe the impacts of quercetin on ferroptosis and SIRT3/AMPK/mTOR-mediated autophagy. METHODS:SIRT3 knock out or overexpressing SCC15 cell line was generated, treated with indicated drugs, and malondialdehyde (MDA) and ROS levels were measured. Roles of SIRT3 in regulating autophagy-mediated ferroptosis were assessed by immunoprecipitation and Western blotting. RESULTS:SIRT3 overexpression increased levels of MDA and ROS, reducing cell viability, and SIRT3 knockout produced the opposing effect. SIRT3 overexpression upregulated ATG16L1 expression and the conversion of LC3-Ⅰ to LC3-Ⅱ, triggering autophagy. Suppression of autophagy by ATG16L1 knockout impaired SIRT3-triggered ferroptosis. Use of an AMPK inhibitor antagonized the induction of ferroptosis by SIRT3 in SCC15 cells, indicating the involvement of the AMPK/mTOR pathway. Additionally, quercetin significantly increased the levels of SIRT3, p-AMPK, ATG16L1, and the ratio of LC3-Ⅱ/Ⅰ, but reduced cell viability and p-mTOR in SCC15 cells. Autophagy and AMPK inhibitors, or SIRT3 deletion significantly antagonized the impacts of quercetin on the autophagy-mediated ferroptosis in cancer cells. DISCUSSION:SIRT3 overexpression activated the AMPK/mTOR pathway and triggered ATG16L1-mediated autophagy, promoting ferroptosis in SCC15 cells, and we proposed that quercetin may be a promising therapeutic drug for OSCC.
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2区Q1影响因子: 2.9
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75. The effects and mechanisms of heat stress on mammalian oocyte and embryo development.
期刊:Journal of thermal biology
日期:2024-08-03
DOI :10.1016/j.jtherbio.2024.103927
The sum of nonspecific physiological responses exhibited by mammals in response to the disruption of thermal balance caused by high-temperature environments is referred to as heat stress (HS). HS affects the normal development of mammalian oocyte and embryos and leads to significant economic losses. Therefore, it is of great importance to gain a deep understanding of the mechanisms underlying the effects of HS on oocyte and embryonic development and to explore strategies for mitigating or preventing its detrimental impacts in the livestock industry. This article provides an overview of the negative effects of HS on mammalian oocyte growth, granulosa cell maturation and function, and embryonic development. It summarizes the mechanisms by which HS affects embryonic development, including generation of reactive oxygen species (ROS), endocrine disruption, the heat shock system, mitochondrial autophagy, and molecular-level alterations. Furthermore, it discusses various measures to ameliorate the effects of HS, such as antioxidant use, enhancement of mitochondrial function, gene editing, cultivating varieties possessing heat-resistant genes, and optimizing the animals'rearing environment. This article serves as a valuable reference for better understanding the relationship between HS and mammalian embryonic development as well as for improving the development of mammalian embryos and economic benefits under HS conditions in livestock production.
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2区Q1影响因子: 2.5
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76. Effect of glutathione addition on vitrification of ovine oocytes.
期刊:Theriogenology
日期:2025-03-28
DOI :10.1016/j.theriogenology.2025.117412
The exogenous antioxidants are commonly employed to mitigate vitrification-induced oxidative damage. Glutathione (GSH), a vital antioxidant, plays a significant role in scavenging free radicals, providing antioxidant protection, and maintaining cellular integrity. This study aimed to investigate the effects of GSH supplementation on the vitrification of ovine oocytes. To identify the optimal concentration of exogenous GSH supplementation, the impacts of 2 mM, 4 mM, and 8 mM GSH on the survival and fragmentation of oocytes were evaluated after vitrification. In addition, immunofluorescence (IF) staining was employed to evaluate spindle morphology, chromosome distribution, cortical granule distribution, mitochondrial function, and reactive oxygen species (ROS) levels. The levels of ATP and NADPH, along with the ratio of GSH/GSSH, were also examined. Additionally, evaluations of in vitro fertilization were carried out. The results of oocyte survival rates and fragmentation rates identified that the addition of 4 mM GSH to the vitrification solution was the optimal concentration. The assessment of spindle morphology, chromosome distribution, cortical granule distribution, mitochondrial function, ROS production, ATP activity, and NADPH levels, as well as the GSH/GSSH ratio, confirm the beneficial effect of GSH supplementation against the vitrification-induced oxidative damage. Lastly, incorporating GSH into the vitrification process enhanced the developmental potential of oocytes, resulting in higher cleavage rates, increased blastocyst rates, and improved quality of blastocysts. Overall, this research uncovered the mechanisms through which GSH mitigates the oxidative damage induced by vitrification, thereby leading to the optimization of the vitrification technique for ovine oocytes.
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4区Q2影响因子: 3.5
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77. Melatonin protects porcine oocytes from gossypol-induced meiosis defects via regulation of SIRT1-mediated mitophagy.
期刊:Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
日期:2024-11-20
DOI :10.1016/j.fct.2024.115122
Cottonseed meal (CSM) is an ideal source of protein feed ingredients. However, the gossypol contained in it has toxic effects on animals, limiting its use in livestock production. The underlying mechanisms remain largely unknown. This study aimed to investigate the adverse effects of gossypol exposure and assess whether melatonin, a natural antioxidant, could alleviate oocyte damage induced by gossypol. Porcine cumulus oocyte complexes (COCs) were treated with gossypol alone or co-treated with melatonin for 44 h during in vitro maturation. The results demonstrated that gossypol exposure induced oxidative stress and mitochondrial dysfunction, leading to oocyte maturation failure. Conversely, melatonin co-treatment mitigated these detrimental effects, by promoting oocyte mitophagy, as evidenced by the upregulation of PINK1, Parkin, and LC3 expressions, along with the downregulation of P62. Further investigation revealed that gossypol treatment significantly decreased SIRT1 protein expression, while melatonin co-treatment markedly increased it. Using the SIRT1 inhibitor Ex527 confirmed that melatonin enhances mitophagy through SIRT1, improving mitochondrial function and rescuing oocyte maturation. This study revealed the potential harm of gossypol on mammalian reproductive health, provided experimental reference for the protective effect of melatonin, and provided theoretical basis for the effective prevention and treatment of reproductive damage caused by gossypol.
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3区Q2影响因子: 3.2
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78. Acrylamide Exposure Impairs Ovarian Tricarboxylic Acid Cycle and Reduces Oocyte Quality in Mouse.
期刊:Environmental toxicology
日期:2024-07-31
DOI :10.1002/tox.24390
Acrylamide (AAM), a compound extensively utilized in various industrial applications, has been reported to induce toxic effects across multiple tissues in living organisms. Despite its widespread use, the impact of AAM on ovarian function and the mechanisms underlying these effects remain poorly understood. Here, we established an AAM-exposed mouse toxicological model using 21 days of intragastric AAM administration. AAM exposure decreased ovarian coefficient and impaired follicle development. Further investigations revealed AAM would trigger apoptosis and disturb tricarboxylic acid cycle in ovarian tissue, thus affecting mitochondrial electron transport function. Moreover, AAM exposure decreased oocyte and embryo development potential, mechanically associated with pericentrin and phosphorylated Aurora A cluster failure, leading to meiotic spindle assembly defects. Collectively, these results suggest that AAM exposure may lead to apoptosis, glucose metabolic disorders, and mitochondrial dysfunction in ovary tissue, ultimately compromising oocyte quality.
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1区Q1影响因子: 5.1
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79. Metformin alleviates cryoinjuries in porcine oocytes by reducing membrane fluidity through the suppression of mitochondrial activity.
期刊:Communications biology
日期:2024-08-01
DOI :10.1038/s42003-024-06631-6
Plasma membrane damage in vitrified oocytes is closely linked to mitochondrial dysfunction. However, the mechanism underlying mitochondria-regulated membrane stability is not elucidated. A growing body of evidence indicates that mitochondrial activity plays a pivotal role in cell adaptation. Since mitochondria work at a higher temperature than the constant external temperature of the cell, we hypothesize that suppressing mitochondrial activity would protect oocytes from extreme stimuli during vitrification. Here we show that metformin suppresses mitochondrial activity by reducing mitochondrial temperature. In addition, metformin affects the developmental potential of oocytes and improves the survival rate after vitrification. Transmission electron microscopy results show that mitochondrial abnormalities are markedly reduced in vitrified oocytes pretreated with metformin. Moreover, we find that metformin transiently inhibits mitochondrial activity. Interestingly, metformin pretreatment decreases cell membrane fluidity after vitrification. Furthermore, transcriptome results demonstrate that metformin pretreatment modulates the expression levels of genes involved in fatty acid elongation process, which is further verified by the increased long-chain saturated fatty acid contents in metformin-pretreated vitrified oocytes by lipidomic profile analysis. In summary, our study indicates that metformin alleviates cryoinjuries by reducing membrane fluidity via mitochondrial activity regulation.
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3区Q1影响因子: 4.9
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80. Disorder of Biological Quality and Autophagy Process in Bovine Oocytes Exposed to Heat Stress and the Effectiveness of In Vitro Fertilization.
期刊:International journal of molecular sciences
日期:2023-07-06
DOI :10.3390/ijms241311164
The main problem in dairy herds is reproductive disorders, which are influenced by many factors, including temperature. Heat stress reduces the quality of oocytes and their maturation through the influence of, e.g., mitochondrial function. Mitochondria are crucial during oocyte maturation as well as the process of fertilization and embryonic development. Disturbances related to high temperature will be increasingly observed due to global warming. In present studies, we have proven that exposure to high temperatures during the cleaving of embryos statistically significantly (at the level of < 0.01) reduces the percentage of oocytes that cleaved and developed into blastocysts eight days after insemination. The study showed the highest percentage of embryos that underwent division in the control group (38.3 °C). The value was 88.10 ± 6.20%, while the lowest was obtained in the study group at 41.0 °C (52.32 ± 8.40%). It was also shown that high temperature has a statistically significant ( < 0.01) effect on the percentage of embryos that developed from the one-cell stage to blastocysts. The study showed that exposure to a temperature of 41.0 °C significantly reduced the percentage of embryos that split relative to the control group (38.3 °C; 88.10 ± 6.20%). Moreover, it was noted that the highest tested temperature limits the development of oocytes to the blastocyst stage by 5.00 ± 9.12% compared to controls (33.33 ± 7.10%) and cleaved embryos to blastocysts by 3.52 ± 6.80%; the control was 39.47 ± 5.40%. There was also a highly significant ( < 0.0001) effect of temperature on cytoplasmic ROS levels after 6 and 12 h IVM. The highest level of mitochondrial ROS was found in the group of oocytes after 6 h IVM at 41.0 °C and the lowest was found in the control group. In turn, at 41.0 °C after 12 h of IVM, the mitochondrial ROS level had a 2.00 fluorescent ratio, and the lowest in the group was 38.3 °C (1.08). Moreover, with increasing temperature, a decrease in the expression level of both LC3 and SIRT1 protein markers was observed. It was proved that the autophagy process was impaired as a result of high temperature. Understanding of the cellular and molecular responses of oocytes to elevated temperatures will be helpful in the development of heat resistance strategies in dairy cattle.
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3区Q1影响因子: 3.3
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81. Pre-culture with transferrin-Fe before in vitro maturation improves the developmental competence of porcine oocytes matured in vitro.
期刊:Reproductive medicine and biology
日期:2023-08-04
DOI :10.1002/rmb2.12529
Purpose:Since the developmental competence of oocytes cultured after in vitro maturation (IVM) is low, it is necessary to improve the IVM method for efficient offspring production. In this study, we revealed that transferrin (TF)-Fe was accumulated in follicular fluid with increasing the follicular diameter, and that TF receptor (TFR1) was localized in granulosa cells of pig. Thus, we hypothesized that TF-Fe would be a factor in the induction of developmental competence of porcine oocytes. Methods:To mimic the follicular development environment, cumulus-oocyte complexes (COCs) were cultured in pre-IVM medium (low dose of FSH) without or with Holo-TF (monoferric or diferric TF) or Apo-TF (non-iron bond TF). After pre-IVM without or with Holo-TF, COCs were cultured in IVM medium (high dose of FSH and EGF) without or with Holo-TF. Results:Cultivation with Holo-TF increased the expression of follicular development maker ( and ), E2 production, and proliferative activity of cumulus cells, whereas cultivation with Apo-TF did not show these positive effects. The treatment with Holo-TF during pre-IVM, but not during IVM, dramatically induced oocyte maturation with increasing the blastocyst rate. Conclusion:We succeeded in showing for the first time that the cultivation with Holo-TF in pre-IVM can produce embryos in pig with high efficiency.
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4区Q2影响因子: 1.9
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82. Effects of dietary quercetin on retrieved mouse oocytes and in vitro fertilization outcomes.
期刊:JBRA assisted reproduction
日期:2025-03-12
DOI :10.5935/1518-0557.20240073
OBJECTIVE:To investigate the effects of dietary quercetin on the retrieved mouse oocytes and IVF outcomes. METHODS:Female mice were divided into two groups. Mice were given 0.2 mL water without (control group) or with quercetin 30 mg/kg (quercetin group) orally via gavage, once a day for 21 consecutive days. After that female mice were superovulated for in vitro fertilization. We observed the effect of dietary quercetin on the number of retrieved oocytes, oocyte degeneration rate, fertilization rate, blastocyst formation rate, and blastocyst cell numbers. RESULTS:There was no difference in the number of retrieved oocytes per mouse (27.3±6.7 and 27.2±5.8), oocyte fragmentation rate (28.4% and 25.0%), fertilization rate (47.4% and 50.6%) and blastocyst formation rate (34.8% and 34.7%) in the quercetin group compared to the control group. The proportion of hatching and hatched blastocyst was significantly lower in the quercetin group (17.2% and 27.8%, p=0.004) and significantly lower numbers of cells in TE (47.4±15.3 and 57.2±17.7) and total cells (66.2±18.5 and 77.5±20.7) compared to the control group (p=0.001). CONCLUSIONS:Dietary quercetin supplementation has a detrimental effect on mouse embryo quality. Moreover, it did not show any beneficial effect on the ovary in both quantity and quality. This finding raises awareness of the general use of dietary quercetin supplements in infertile females.
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2区Q1影响因子: 6.6
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83. Porcine Granulosa-Cell-Derived Exosomes Enhance Oocyte Development: An In Vitro Study.
期刊:Antioxidants (Basel, Switzerland)
日期:2024-03-14
DOI :10.3390/antiox13030348
Recent studies have established that exosomes (EXs) derived from follicular fluid (FF) can promote oocyte development. However, the specific sources of these EXs and their regulatory mechanisms remain elusive. It is universally acknowledged that oocyte development requires signal communication between granulosa cells (GCs) and oocytes. However, the role of GC-secreted EXs and their functions are poorly understood. This study aimed to investigate the role of porcine granulosa-cell-derived exosomes (GC-EXs) in oocyte development. In this study, we constructed an in vitro model of porcine GCs and collected and identified GC-EXs. We confirmed that porcine GCs can secrete EXs and investigated the role of GC-EXs in regulating oocyte development by supplementing them to cumulus-oocyte complexes (COCs) cultured in vitro. Specifically, GC-EXs increase the cumulus expansion index (CEI), promote the expansion of the cumulus, alleviate reactive oxygen species (ROS), and increase mitochondrial membrane potential (MMP), resulting in improved oocyte development. Additionally, we conducted small RNA sequencing of GC-EXs and hypothesized that miR-148a-3p, the highest-expressed microRNA (miRNA), may be the key miRNA. Our study determined that transfection of miR-148a-3p mimics exerts effects comparable to the addition of EXs. Meanwhile, bioinformatics prediction, dual luciferase reporter gene assay, and RT-qPCR identified DOCK6 as the target gene of miR-148a-3p. In summary, our results demonstrated that GC-EXs may improve oocyte antioxidant capacity and promote oocyte development through miR-148a-3p by targeting DOCK6.
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4区Q4影响因子: 1.4
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84. Effects of oxygen concentrations on developmental competence and transcriptomic profile of yak oocytes.
作者:Li Ruizhe , Luo Yuzhu , Xu Jingtao , Sun Yonggang , Ma Zhijie , Chen Shengmei
期刊:Zygote (Cambridge, England)
日期:2020-08-10
DOI :10.1017/S0967199420000337
Oxygen concentration influences oocyte quality and subsequent embryo development, but it remains unclear whether oxygen concentrations affect the developmental competence and transcriptomic profile of yak oocytes. In this study, we investigated the effects of different oxygen concentrations (5% versus 20%) on the developmental competence, reactive oxygen species (ROS) levels, glutathione (GSH) content, and transcriptomic profile of yak oocytes. The results showed that a low oxygen concentration significantly increased the maturation rate of yak oocytes (81.2 ± 2.2% vs 75.9 ± 1.3%) and the blastocyst quality of yak in vitro fertilized embryos. Analysis of ROS and GSH showed that a low oxygen concentration reduced ROS levels and increased the content of GSH (75.05 ± 7.1 ng/oocyte vs 50.63 ± 5.6 ng/oocyte). Furthermore, transcriptomic analysis identified 120 differentially expressed genes (DEGs) between the two groups of oocytes. Gene enrichment analysis of the DEGs indicated multiple cellular processes, including oxidative phosphorylation, transcription regulation, mitochondrial regulation, oestrogen signalling pathway, HIF-1 signalling pathway, TNF signalling pathway, were involved in the response to oxygen concentration alterations. Taken together, these results indicated that a low oxygen concentration improved the developmental competence of yak oocytes.
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2区Q1影响因子: 3.6
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85. Eif4enif1 haploinsufficiency disrupts oocyte mitochondrial dynamics and leads to subfertility.
期刊:Development (Cambridge, England)
日期:2023-12-13
DOI :10.1242/dev.202151
Infertility affects couples worldwide. Premature ovarian insufficiency (POI) refers to loss of ovarian function before 40 years of age and is a contributing factor to infertility. Several case studies have reported dominant-inherited POI symptoms in families with heterozygous EIF4ENIF1 (4E-T) mutations. However, the effects of EIF4ENIF1 haploinsufficiency have rarely been studied in animal models to reveal the underlying molecular changes related to infertility. Here, we demonstrate that Eif4enif1 haploinsufficiency causes mouse subfertility, impairs oocyte maturation and partially arrests early embryonic development. Using dual-omic sequencing, we observed that Eif4enif1 haploinsufficiency significantly altered both transcriptome and translatome in mouse oocytes, by which we further revealed oocyte mitochondrial hyperfusion and mitochondria-associated ribonucleoprotein domain distribution alteration in Eif4enif1-deficient oocytes. This study provides new insights into the molecular mechanisms underlying clinical fertility failure and new avenues to pursue new therapeutic targets to address infertility.
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2区Q2影响因子: 5.2
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86. Elucidating the Role of Sirtuin 3 in Mammalian Oocyte Aging.
期刊:Cells
日期:2024-09-22
DOI :10.3390/cells13181592
The field of reproductive biology has made significant progress in recent years, identifying specific molecular players that influence oocyte development and function. Among them, sirtuin 3 (SIRT3) has attracted particular attention for its central role in mediating mitochondrial function and cellular stress responses in oocytes. So far, studies have demonstrated that the knockdown of SIRT3 leads to a decrease in blastocyst formation and an increase in oxidative stress within an embryo, underscoring the importance of SIRT3 in maintaining the cellular redox balance critical for embryonic survival and growth. Furthermore, the literature reveals specific signaling pathways, such as the SIRT3- Glycogen synthase kinase-3 beta (GSK3β) deacetylation pathway, crucial for mitigating oxidative stress-related anomalies in oocyte meiosis, particularly under conditions like maternal diabetes. Overall, the emerging role of SIRT3 in regulating oocyte mitochondrial function and development highlights the critical importance of understanding the intricate connections between cellular metabolism, stress response pathways, and overall reproductive health and function. This knowledge could lead to the development of novel strategies to support oocyte quality and fertility, with far-reaching implications for assisted reproductive technologies and women's healthcare. This commentary aims to provide an overview of the importance of SIRT3 in oocytes by synthesizing results from a multitude of studies. The aim is to elucidate the role of SIRT3 in oocyte development, maturation, and aging and to identify areas where further research is needed.
ABSTRACT:Epilepsy is a prevalent neurological disorder in which hippocampal neuronal damage, particularly ferroptosis, plays a critical role. Previous studies have shown that hypoxia-inducible factor 1α is considered an important regulator of cellular stress responses and has been confirmed to play a critical role in the occurrence of various diseases. However, the mechanisms by which hypoxia-inducible factor 1α is related to epilepsy and neuronal ferroptosis remain unclear. In this study, we used a pentylentetrazole-induced chronic epilepsy mouse model and treated the mice with intraperitoneal administration of PX-478, a hypoxiainducible factor-1α inhibitor. Our results showed that PX-478 significantly prolonged the latency of epilepsy, reduced seizure severity, and shortened seizure duration. PX-478 also alleviated neuronal damage in the hippocampal CA1 and CA2 regions, reduced levels of reactive oxygen species and malondialdehyde, and increased levels of superoxide dismutase, catalase, and glutathione peroxidase. Transmission electron microscopy showed that PX-478 treatment reduced mitochondrial damage in the hippocampal neurons of epileptic mice, and significantly improved mitochondrial length and area. Additionally, PX-478 preferentially reduced Fe 2+ levels and the expression of cyclooxygenase-2, ferritin heavy chain 1 and transferrin in the hippocampus of epileptic mice. It also inhibited the activity of the hypoxia-inducible factor 1α/heme oxygenase-1 pathway. In summary, these findings suggest that PX-478 has the potential to treat epilepsy by inhibiting the hypoxia-inducible factor 1α/heme oxygenase-1 pathway, alleviating oxidative stress, and reducing ferroptosis in hippocampal neurons.
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1区Q1影响因子: 4.4
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88. Role of hypoxia-inducible-factor-1α (HIF-1α) in ferroptosis of adipose tissue during ketosis.
期刊:Journal of dairy science
日期:2024-07-26
DOI :10.3168/jds.2024-24822
Postpartum cows experience lipolysis in adipose tissue due to negative energy balance, and accumulation of free fatty acids leads to metabolic stress in adipose tissue. Ferroptosis is a type of cell death triggered by excessive buildup of iron-dependent lipid peroxides and is involved in the occurrence and development of various metabolic diseases in nonruminants. However, whether ferroptosis occurs in the adipose tissue of ketotic cows and the regulatory mechanisms behind ferroptosis are still unclear. Despite multiple studies demonstrating the significant involvement of hypoxia-inducible-factor-1α (HIF-1α) in regulating cellular dysfunction, its specific function in the adipose tissue of ketotic dairy cows remains uncertain, particularly its regulation of oxidative stress and ferroptosis. This study aimed to explore the effect of HIF-1α on oxidative stress and ferroptosis in bovine subcutaneous adipose tissue and isolated adipocytes. The adipose tissue of clinical ketosis cows (n = 15) with a serum BHB concentration of 3.13 mM (interquartile range = 0.14) and healthy cows (n = 15) with a serum BHB concentration of and 0.58 mM (interquartile range = 0.13) was collected. The results showed that the concentrations of lipid peroxidation malondialdehyde (MDA), reactive oxygen species (ROS), Fe, and total iron were increased in adipose tissue of cows with ketosis, but the contents of glutathione (GSH) were reduced. Furthermore, the protein levels of HIF-1α, heme oxygenase 1 (HMOX1), catalase (CAT), superoxide dismutase 1 (SOD1), acyl-CoA synthetase 4, and nuclear factor erythroid-derived 2-like 2 (NFE2L2) exhibited higher abundance in adipose tissue obtained from cows with ketosis, whereas the protein abundance of solute carrier family 7 member 11 (SLC7A11), glutamate-cysteine ligase catalytic subunit (GCLC), kelch-like ECH-associated protein 1, glutamate-cysteine ligase regulatory subunit (GCLM), and glutathione peroxidase 4 (GPX4) were lower. To simulate the ferroptosis state of adipose tissue in ketotic cows, primary bovine adipocytes were isolated from the adipose tissue of healthy cows and cultured with erastin to construct the ferroptosis model. Adipocytes were cultured with either an adenovirus overexpressing HIF-1α or small interfering RNA targeting HIF for 48 h, followed by exposure to erastin (1 μM) for 24 h. Treatment with erastin led to higher protein abundance of CAT, SOD1, NFE2L2 and HMOX1, and it inhibited the protein expression levels of GCLC, SLC7A11, GCLM, GPX4, and kelch-like ECH-associated protein 1. Furthermore, erastin treatment elevated the levels of ROS, MDA, Fe, and total iron and reduced the content of GSH. The overexpression of HIF-1α reversed the erastin-induced decreases in the protein abundance of GPX4 and SLC7A11, as well as the levels of MDA, ROS, Fe, and total iron, while significantly increasing protein abundance and content of CAT, SOD1, NFE2L2, HMOX1, GCLC, GCLM, GPX4, SLC7A11, and GSH. Conversely, the silencing of HIF-1α further exacerbated the erastin-induced levels of MDA, ROS, Fe, and total iron, while inhibiting the upregulation of SOD1, CAT, NFE2L2 and HMOX1. Collectively, these findings suggest that activation of HIF-1α may function as an adaptive mechanism to mitigate ferroptosis and alleviate oxidative stress in adipose tissue.
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4区Q2影响因子: 1.3
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89. Hypoxia-Inducible Factor 1-Alpha (HIF-1α): An Essential Regulator in Cellular Metabolic Control.
期刊:Cureus
日期:2024-07-04
DOI :10.7759/cureus.63852
The element that causes hypoxia when the von Hippel-Lindau (VHL) protein is not functioning is hypoxia-inducible factor 1-alpha (HIF-1α), which is the essential protein linked to cell control under hypoxia. Consequently, in situations where cells are oxygen-deficient, HIF-1α carries out a variety of essential functions. Citations to relevant literature support the notion that HIF-1α regulates the mitochondrial and glycolytic pathways, as well as the transition from the former to the latter. Cells with limited oxygen supply benefit from this change, which is especially beneficial for the inhibition of the mitochondrial electron transport chain and enhanced uptake of glucose and lactate. During hypoxic stress, HIF-1α also controls proline and glycolytic transporters such as lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1). These mechanisms help the cell return to homeostasis. Therefore, through metabolic change promoting adenosine triphosphate (ATP) synthesis and reducing reactive oxygen species (ROS) creation, HIF-1α may have a role in reducing oxidative stress in cells. This evidence, which describes the function of HIF-1α in many molecular pathways, further supports the notion that it is prognostic and that it contributes to hypoxic cell adaption. Understanding more about disorders, including inflammation, cancer, and ischemia, is possible because of HIF-1α's effect on metabolic changes. Gaining knowledge about the battle between metabolism, which is directed by HIF-1α, would help advance the research on pathophysiological situations involving dysregulated hypoxia and metabolism.
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2区Q1影响因子: 6.6
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90. Hypoxia-Inducible Factor 1α Affects Yak Oocyte Maturation and Early Embryonic Development by Regulating Autophagy.
期刊:Antioxidants (Basel, Switzerland)
日期:2024-07-14
DOI :10.3390/antiox13070840
In animal assisted reproductive technology, the production of high-quality oocytes is crucial. The yak, having lived in the Qinghai-Tibet Plateau for an extended period, has reproductive cells that are regulated by hypoxia-inducible factor 1α (HIF-1α). This study aimed to investigate the impact of HIF-1α on yak oocyte maturation and early embryonic development in vitro through the regulation of autophagy. The in vitro maturation process of yak oocytes involved the addition of the HIF-1α inducer DFOM and the inhibitor LW6 to examine their effects on yak oocyte maturation, early embryonic development, cell autophagy, cytochrome P450s (CYP450s) enzyme expression, and cumulus diffusion factors. The findings revealed that DFOM significantly upregulated the expression of HIF-1α, resulting in increased the cumulus diffusion area, elevated first polar body expulsion rate of oocytes, enhanced mitochondrial and actin levels, decreased ROS production, and reduced early apoptosis levels of oocytes. Moreover, DFOM promoted the expression of autophagy-related proteins, CYP450s enzymes, and cumulus diffusion factors, thereby enhancing oocyte maturation and early embryonic development. Conversely, LW6 exhibited opposite effects. The inhibition of autophagy levels with 3-MA during DFOM treatment yielded similar outcomes. Furthermore, reducing autophagy led to increased apoptosis levels at all stages of early embryonic development, as well as a significant decrease in total cell number and ICM/TE ratio of blastocysts. Studies have shown that during the in vitro maturation of yak oocytes, HIF-1α can affect the cumulus expansion area of oocytes by regulating autophagy, the first polar body excretion rate, mitochondrial level, actin level, ROS and early apoptosis level, the CYP450s enzyme, and the expression of cumulus expansion factors, thereby improving the in vitro maturation and early embryonic development of yak oocytes. These findings offer valuable insights into the reproductive regulation mechanism of yaks in hypoxic environments and suggest potential strategies for the advancement of yak assisted reproductive technology.
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3区Q2影响因子: 3.4
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91. Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex.
In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC. Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles were cultured with 0, 0.22, 2.2, 22, 220, and 2200 nM BPA for 2 h. An additional 16-h incubation with epidermal growth factor (EGF) was performed to promote the occurrence of meiotic resumption and progression to metaphase II. Without EGF stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the percentage of oocytes that remained at the anaphase and telophase stages, and decreased the percentage of oocytes reaching the metaphase II stage. Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor) exerted effects on meiotic division similar to those exerted by BPA. These data suggest that BPA accelerates meiotic progression, leading to impaired prophase I-to-metaphase II transition, and that this adverse effect is correlated with reduced bidirectional communication in the COC.
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2区Q1影响因子: 2.5
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92. Ferric ammonium citrate regulates iron death in mature porcine oocytes and their embryonic development in vitro through the NRF2 signaling pathway.
期刊:Theriogenology
日期:2024-11-02
DOI :10.1016/j.theriogenology.2024.10.033
Iron death is a novel type of programmed cell death caused by excessive accumulation of iron-dependent lipid peroxidation products; however, the function of iron death during porcine oocyte maturation and embryo growth is poorly understood. This study was conducted to investigate the mechanism of ferric ammonium citrate (FAC) in regulating iron death in mature oocytes in vitro through the NRF2 signaling pathway, and subsequent embryonic development. The experiment was divided into four groups: 0 (control group), 2, 5, and 10 μM FAC. Western blotting (WB), reactive oxygen species (ROS)assays, mitochondrial membrane potential (MMP) assays, and Quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the maturation of porcine oocytes in vitro, the protein content of nuclear transcription factor E2-related factor 2 (Nrf2), the distribution of mitochondria, the level of oxidative stress, and the development of embryos fertilized in vitro. The results showed that with increasing FAC concentrations, the oocyte maturation rate in vitro, Nrf2 protein content, MMP, and cleavage rates of in vitro fertilized embryos decreased (significantly in the 5 μM group); the oxidative stress level was significantly increased; the transcript levels of Nrf2, GPX4, and FTH1 mRNAs were significantly decreased; the expression of ACSL4 was significantly upregulated (P < 0.05); and the blastocyst rate of embryos fertilized in vitro was reduced (significantly in the 2 μM group). In conclusion, FAC can regulate Nrf2 protein levels in porcine oocytes matured in vitro to induce iron death, affecting the maturation rate of oocytes, distribution of mitochondria, level of oxidative stress, expression of iron-death-related genes, and development of embryos after in vitro fertilization.