Contamination status of bisphenol A and its analogues (bisphenol S, F and B) in foodstuffs and the implications for dietary exposure on adult residents in Zhejiang Province.
Zhou Jian,Chen Xiao-Hong,Pan Sheng-Dong,Wang Jun-Lin,Zheng Yi-Bin,Xu Jiao-Jiao,Zhao Yong-Gang,Cai Zeng-Xuan,Jin Mi-Cong
An effective method has been developed for the simultaneous determination of four bisphenols (bisphenol A, S, F and B) in various foodstuffs. The contaminants were extracted by QuEChERS-based strategy and subjected to ion-exchange solid-phase extraction for further clean-up. The critical variables were screened by Plackett-Burman design and then optimized by central composite design. Under the optimized conditions, satisfactory accuracy (recoveries 76%-116%) and precision (RSDs < 12%) were achieved. The established method was then used to assess the contamination status of 379 real samples. Bisphenol A was demonstrated to be the predominant bisphenol with highest incidence (79.7%) and average concentration (14.3 μg/kg). The positive rates (mean concentration) of bisphenol S, F and B were 37.7% (1.6 μg/kg), 26.9% (1.4 μg/kg) and 0.0% (not detected), respectively. Finally, the daily dietary intakes of ∑bisphenolsfor adult residents were estimated (55.9-76.1 ng/kg bw/day) according to the contamination concentrations and the daily recommended intakes.
Effects of bisphenol A on ovarian follicular development and female germline stem cells.
Zhu Xiaoqin,Tian Geng G,Yu Baoli,Yang Yanzhou,Wu Ji
Archives of toxicology
Bisphenol A (BPA), one of the most frequently detected emerging pollutants in the environment, has been implicated in adverse effects in male and female reproduction at extremely low concentrations. This study aimed to investigate the effects and potential mechanism of BPA on mouse ovarian follicular development and female germline stem cells (FGSCs). Female CD-1 adult mice were administered gradient concentrations of BPA (12.5, 25, and 50 mg/kg/day) by intraperitoneal injection. We found that the number of atretic ovarian follicles was significantly increased at high BPA concentrations. Additionally, the numbers of primordial follicles, primary follicles, and corpus luteum (CL) were significantly reduced at high BPA concentrations. Interestingly, the number of FGSCs was remarkably reduced in BPA-treated ovaries. Furthermore, the increased apoptotic rate of FGSCs in vitro was triggered by BPA accompanied by increased BPA concentrations. To investigate the mechanism of BPA in ovarian follicular development, 193 differentially expressed proteins were identified in BPA-treated ovaries by the isobaric tags for relative and absolute quantification-coupled 2D liquid chromatography-mass spectrometry technique. A total of 106 proteins were downregulated and 85 proteins were upregulated. Among these proteins, the apoptosis-related protein SAFB-like transcriptional modulator (SLTM) was remarkably upregulated, and this result was consistent with western blotting. Taken together, our results suggest that an ovarian follicular development, especially, the development of primordial follicles, primary follicles, and the CL, is inhibited by high BPA concentrations, and the ovarian follicle atresia is initiated by BPA through upregulated expression of SLTM. Furthermore, BPA induces apoptosis of cultured FGSCs. The effect of BPA on ovarian follicular development and FGSCs, especially the effect on FGSCs, suggests a novel mechanism of how BPA causes female infertility.
Comparative effects of Bisphenol S and Bisphenol A on the development of female reproductive system in rats; a neonatal exposure study.
Ahsan Nida,Ullah Hizb,Ullah Waheed,Jahan Sarwat
Bisphenol A (BPA) has been well documented for its endocrine disrupting potential however, very little is known about endocrine disrupting abilities of bisphenol S (BPS). The present study aimed to compare the endocrine disrupting potentials of BPS with BPA, using female rats as an experimental animal model. On postnatal day 1 (PND 1) female pups born were randomly assigned to seven different treatments. Control group received subcutaneous injection of castor oil (50 μL) from PND 1 to PND 10. Three groups of female pups were injected subcutaneously with different concentrations (0.5, 5 and 50 mg/kg in 50 μL castor oil) of BPS, while remaining three groups were treated with 0.5, 5 and 50 mg/kg BPA. Highest doses treatments of both compounds resulted in delayed puberty onset and altered estrous cyclicity. Final body weight was significantly high in the highest dose treated groups of both BPS and BPA. Gonadosomatic index, absolute and relative weight of uteri was significantly reduced in BPS (5 and 50 mg/kg) and BPA (5 and 50 mg/kg) treated groups than control. Plasma concentrations of testosterone and estradiol were significantly increased, while plasma progesterone, Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) concentrations were significantly reduced in highest doses treated groups. Dose dependent increase in the number of cystic follicles in the ovaries was evident along with an increase in the number of atratic follicles. The results suggest that neonatal exposure to higher concentrations of BPS can lead to BPA like structural and endocrine alterations in female rats.
Bisphenol A exposure disturbs the bone metabolism: An evolving interest towards an old culprit.
Thent Zar Chi,Froemming Gabriele Ruth Anisah,Muid Suhaila
Bisphenol A (BPA) (2,2,-bis (hydroxyphenyl) propane), a well-known endocrine disruptor (ED), is the exogenous chemical that mimic the natural endogenous hormone like oestrogen. Due to its extensive exposure to humans, BPA is considered to be a major toxicological agent for general population. Environmental exposure of BPA results in adverse health outcomes including bone loss. BPA disturbs the bone health by decreasing the plasma calcium level and inhibiting the calcitonin secretion. BPA also stimulated differentiation and induced apoptosis in human osteoblasts and osteoclasts. However, little is known about the underlying mechanisms of the untoward effect of BPA against bone metabolism. The present review gives an overview on the possible mechanisms of BPA towards bone loss. The previous literature shows that BPA exerts its toxic effect on bone cells by binding to the oestrogen related receptor-gamma (ERγ), reducing the bone morphogenic protein-2 (BMP-2) and alkaline phosphatase (ALP) activities. BPA interrupts the bone metabolism via RANKL, apoptosis and Wnt/β-catenin signaling pathways. It is, however, still debated on the exact underlying mechanism of BPA against bone health. We summarised the molecular evidences with possible mechanisms of BPA, an old environmental culprit, in bone loss and enlightened the underlying understanding of adverse action of BPA in the society.
Acute effect of bisphenol A: Signaling pathways on calcium influx in immature rat testes.
Gonçalves Renata,Zanatta Ana Paula,Cavalari Fernanda Carvalho,do Nascimento Monica Andressa Wessner,Delalande-Lecapitaine Christelle,Bouraïma-Lelong Hélène,Silva Fátima Regina Mena Barreto
Reproductive toxicology (Elmsford, N.Y.)
We investigated the acute effect of low concentrations of BPA on calcium influx and the mechanism of action of BPA in this rapid response in the rat testis. BPA increased calcium influx at 1 pM and 1 nM at 300 s of incubation, in a similar manner to that of estradiol. At 1 pM, BPA stimulated calcium influx independently of classical estrogen receptors, consistent with a G-protein coupled receptor. This effect also involves the modulation of ionic channels, such as K, TRPV1 and Cl channels. Furthermore, BPA is able to modulate calcium from intracellular storages by inhibiting SERCA and activating IP receptor/Ca channels at the endoplasmic reticulum and activate kinase proteins, such as PKA and PKC. The rapid responses of BPA on calcium influx could, in turn, trigger a cross talk by MEK and p38 activation and also mediate genomic responses.
Renal and hepatic effects following neonatal exposure to low doses of Bisphenol-A and Cs.
Esplugas Roser,LLovet Maria Isabel,Bellés Montserrat,Serra Noemí,Vallvé Joan Carles,Domingo José Luis,Linares Victoria
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
137-Cesium (Cs) is one of the most important distributed radionuclides after a nuclear accident. Humans are usually co-exposed to various environmental toxicants, being Bisphenol-A (BPA) one of them. Exposure to IR and BPA in early life is of major concern, due to the higher vulnerability of developing organs. We evaluate the renal and hepatic effects of low doses of ionizing radiation (IR) and BPA. Sixty male mice (C57BL/6J) were randomly assigned to six experimental groups (n=10) and received a single subcutaneous dose of 0.9% saline solution, Cs and/or BPA on postnatal day 10: control, BPA (25 μg/kgbw), Cs4000 (4000 Bq Cs/kgbw), Cs8000 (8000 Bq Cs/kgbw), BPA/Cs4000 and BPA/Cs8000. At the age of two months, urines (24h) and blood samples were collected from animals of each group to determine biochemical parameters. Finally, kidneys and liver were removed to quantify DNA damage (8-OHdG), as well as to determine CYP1A2 mRNA expression. Data suggest that both BPA and Cs induced renal and liver damage evidenced by oxidative stress. However, when there is a co-exposure, it seems that there are compensatory mechanisms that may reverse the damage induced by each toxic itself. Notwithstanding, more studies are necessary to better understand the synergistic mechanisms behind.
Environmentally relevant levels of bisphenol A affect uterine decidualization and embryo implantation through the estrogen receptor/serum and glucocorticoid-regulated kinase 1/epithelial sodium ion channel α-subunit pathway in a mouse model.
Yuan Mu,Hu Minhao,Lou Yiyun,Wang Qijing,Mao Luna,Zhan Qitao,Jin Fan
Fertility and sterility
OBJECTIVE:To investigate whether bisphenol A (BPA) exposure is associated with uterine decidualization and embryo implantation failure in mice. DESIGN:Experimental animal study and in vitro study. SETTING:University-based infertility center. ANIMAL(S):ICR mice. INTERVENTION(S):Mice treated with different doses of BPA; Ishikawa cells cultured in medium of different concentrations of BPA. MAIN OUTCOME MEASURE(S):Embryo implantation sites, uterine weight, quantitative real-time reverse transcriptase-polymerase chain reaction, Western blot analysis, hematoxylin and eosin staining, and immunohistochemical, cell proliferation, and statistical analyses. RESULT(S):In the experiment of mouse model, administration of 1-100 μg/kg/day of BPA by gavage led to reduction of the number of embryo implantation sites in a dose-dependent manner; 100 μg/kg/day of BPA statistically significantly reduced the number of implantation sites compared with the control group. The uterine weight change (the wet weight of the decidualized uterine horn divided by the wet weight of the undecidualized uterine horn of the mouse) in groups exposed to BPA (100-10,000 μg/kg/day) were statistically significantly lower compared with the control group. Immunohistochemical analysis demonstrated that administration of 100, 1,000, or 10,000 μg/kg/day of BPA by gavage statistically significantly down-regulated the expression of epithelial Na channel α-subunit (ENaCα) in the luminal epithelial cells and desmin in decidual cells of the oil-induced decidualized uterine horns. Administration of 100 μg/kg/day BPA on embryo days 0.5-3.5 by gavage statistically significantly decreased the level of uterine serum and glucocorticoid-regulated kinase 1 (SGK1) protein expression on embryo days 4 and 6. After treatment with 0.001, 0.01, 0.1, or 1.0 μg/mL of BPA for 48 hours, the SGK1, ENaCα, and phospho-SGK1 protein expression of Ishikawa cells was down-regulated, and the effect of BPA on SGK1 could be abrogated by fulvestrant. CONCLUSION(S):Our study provides the first indication that BPA exposure at levels as low as 100 μg/kg/day can impair embryo implantation in mice and BPA can affect decidualization of the uterus in mouse model. Our results suggest that BPA can down-regulate SGK1 and ENaCα protein expression through estrogen receptors in Ishikawa cells.
Mass spectrometry investigation of DNA adduct formation from bisphenol A quinone metabolite and MCF-7 cell DNA.
Zhao Hongzhi,Wei Juntong,Xiang Li,Cai Zongwei
Bisphenol A (BPA) is a widely used additive in the plastic industry and has been reported to have genotoxicity. A hypothesis that BPA may enhance breast cancer risk through the formation of its metabolic intermediate or DNA adduct has been proposed. In this study, breast cancer cell MCF-7 was cultured and the cellular DNA was extracted from the cells. The adducts of bisphenol A 3,4-quinone (BPAQ) with 2'-deoxyguanosine (dG), calf thymus DNA and MCF-7 cell DNA were investigated. DNA adducts were characterized by using electrospray ionization Orbitrap high-resolution mass spectrometry and tandem mass spectrometry. The BPA-DNA adducts of BPAQ with dG, calf thymus and MCF-7 cell DNA were identified as 3-hydroxy-bisphenol A-N7-guanine (3-OH-BPA-N7Gua). The MS/MS fragmentation pathway of 3-OH-BPA-N7Gua was proposed based on obtained accurate mass data. BPA quinone metabolites can react with MCF-7 cell DNA in vitro. The findings provide evidence that BPA might covalently bind to DNA in MCF-7 cells mediated by quinone metabolites, which may increase our understanding of health risk associated with BPA exposure.
Effects of perinatal exposure to bisphenol A on the intraprostatic levels of aromatase and 5α-reductase isozymes in juvenile rats.
Castro Beatriz,Sánchez Pilar,Torres Jesús M,Ortega Esperanza
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
The impact of bisphenol A (BPA) on the prostate gland has taken center stage, with a special focus placed on understanding how BPA affects prostate physiopathology. In this study, we evaluated the ability of lower doses of BPA to induce alterations in 5α-R isozymes and aromatase, in the prostate of juvenile rats exposed during developmental stage. Gestating Wistar rats were treated s.c with either vehicle or BPA (2.4 and 10 μg/kg b.w./day) from gestational day 12 to parturition. Then, male pups were s.c treated from postnatal day 1 through day 21, when they were euthanized and qRT-PCR, western blot and hormone levels determination were performed. We found that BPA at dose of 2.4 and 10 μg/kg b.w./day significantly decreased the mRNA and protein levels of 5α-R2. However, neither 5α-R1 nor 5α-R3 was affected by this exposure. BPA at dose of 10 μg/kg b.w./day significantly increased the mRNA and protein levels of aromatase. BPA also decreased plasma levels of both testosterone and dihydrotestosterone and increased estradiol. These data lend support that low-dose BPA during fetal and neonatal prostate development interfere with in situ estrogen and androgen production in the prostate gland of juvenile rats through the enzymes aromatase and 5α-Reductase.
Opening the black box of endocrine disruption of brain development: Lessons from the characterization of Bisphenol A.
Nesan Dinushan,Sewell Laronna C,Kurrasch Deborah M
Hormones and behavior
Bisphenol A (BPA) is among the best-studied endocrine disrupting chemicals, known to act via multiple steroid hormone receptors to mediate a myriad of cellular effects. Pre-, peri-, and postnatal BPA exposure have been linked to a variety of altered behaviors in multiple model organisms, ranging from zebrafish to frogs to mammalian models. Given that BPA can cross the human placental barrier and has been found in the serum of human fetuses during gestation, BPA has been postulated to adversely affect ongoing neurodevelopment, ultimately leading to behavioral disorders later in life. Indeed, the brain has been identified as a key developmental target for BPA disruption. Despite these known associations between gestational BPA exposure and adverse developmental outcomes, as well as an extensive body of evidence existing in the literature, the mechanisms by which BPA induces its cellular- and tissue-specific effects on neurodevelopmental processes still remains poorly understood at a mechanistic level. In this review we will briefly summarize the effects of gestational BPA exposure on neural developmental mechanisms and resulting behaviors, and then present suggestions for how we might address gaps in our knowledge to develop a fuller understanding of endocrine neurodevelopmental disruption to better inform governmental policy against the use of BPA or other endocrine disruptors.
Bisphenol A (BPA) modulates the expression of endocrine and stress response genes in the freshwater snail Physa acuta.
Morales Mónica,Martínez-Paz Pedro,Sánchez-Argüello Paloma,Morcillo Gloria,Martínez-Guitarte José Luis
Ecotoxicology and environmental safety
Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P. acuta were evaluated at the molecular level by analysing changes in the transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), as well as in genes involved in the stress response, such as hsp70 and hsp90. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that BPA induced a significant increase in the mRNA levels of ER, ERR, and RXR, suggesting that these receptors could be involved in similar pathways or regulation events in the endocrine disruptor activity of this chemical at the molecular level in Gastropoda. Additionally, the hsp70 expression was upregulated after 5 and 72h of BPA exposures, but hsp90 was only upregulated after 5h of BPA exposure. Finally, we assessed the glutathione-S-transferase (GST) activity after BPA treatment and found that it was affected after 48h. In conclusion, these data provide, for the first time, evidences of molecular effects produced by BPA in the endocrine system of Gastropoda, supporting the potential of ER, ERR and RXR as biomarkers to analyse putative EDCs in ecotoxicological studies. Moreover, our results suggest that P. acuta is an appropriate sentinel organism to evaluate the effect of EDCs in the freshwater environment.
Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis.
Rochester Johanna R,Bolden Ashley L,Kwiatkowski Carol F
BACKGROUND:Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans. OBJECTIVES:Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD. DATA SOURCES:Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017. STUDY ELIGIBILITY CRITERIA:For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at <3 months of age for humans, up to postnatal day 35 for rats and up to postnatal day 40 for mice. Exposure could occur either gestationally (via maternal exposure) or directly to the offspring. STUDY APPRAISAL AND SYNTHESIS METHODS:Studies were evaluated using the OHAT risk of bias tool. The effects in humans were assessed qualitatively. For rodents exposed to 20 μg/kg/day BPA, we evaluated the study findings in a random effects meta-analytical model. RESULTS:A review of the literature identified 29 rodent and 3 human studies. A random effects meta-analysis showed significantly increased hyperactivity in male rodents. In humans, early BPA exposure was associated with hyperactivity in boys and girls. LIMITATIONS, CONCLUSIONS, AND IMPLICATIONS OF KEY FINDINGS:We concluded that early life BPA exposure is a presumed human hazard for the development of hyperactivity. Possible limitations of this systematic review include deficiencies in author reporting, exclusion of some literature based on language, and insufficient similarity between human studies. SRs that result in hazard-based conclusions are the first step in assessing and mitigating risks. Given the widespread exposure of BPA and increasing diagnoses of ADHD, we recommend immediate actions to complete such risk analyses and take next steps for the protection of human health. In the meantime, precautionary measures should be taken to reduce exposure in pregnant women, infants and children. The present analysis also discusses potential mechanisms by which BPA affects hyperactivity, and the most effective avenues for future research. SYSTEMATIC REVIEW REGISTRATION NUMBER:Not available.
Spindle abnormalities and chromosome misalignment in bovine oocytes after exposure to low doses of bisphenol A or bisphenol S.
Campen Kelly A,Kucharczyk Katherine M,Bogin Benjamin,Ehrlich Julie M,Combelles Catherine M H
Human reproduction (Oxford, England)
STUDY QUESTION:What are the effects of exposure to bisphenol A (BPA) or bisphenol S (BPS) during IVM on bovine oocyte maturation, spindle morphology and chromosome alignment? SUMMARY ANSWER:Exposure to BPA or BPS during IVM resulted in increased spindle abnormalities and chromosome misalignment, even at very low concentrations. WHAT IS KNOWN ALREADY:BPA is an endocrine disrupting chemical that alters oocyte maturation, spindle morphology and chromosome alignment in a range of species. The use of BPA substitutes, such as BPS, is increasing and these substitutes often display different potencies and mechanisms of action compared with BPA. STUDY DESIGN, SIZE, DURATION:Bovine cumulus-oocyte complexes (COCs) underwent IVM with BPA or BPS for 24 h, together with vehicle-only controls. Overall, 10 different concentrations of BPA or BPS were used ranging from 1 fM to 50 μM in order to detect low dose or non-monotonic effects. An incomplete block design was utilized for the study, with at least three replicates per block. A total of 939 oocytes (250 of which were controls) were used for the BPA experiments, and 432 (110 controls) for the BPS experiments. Following the IVM period, the oocytes were denuded and fixed for immunocytochemistry. PARTICIPANTS/MATERIALS, SETTING, METHODS:Immunocytochemistry was used to label the chromatin, actin, and microtubules in the fixed oocytes. The meiotic stage was assessed using immunofluorescence, and the metaphase-II (MII) oocytes were further assessed for spindle morphology and chromosome alignment (in all MII oocytes regardless of spindle morphology) using immunofluorescence and confocal microscopy. Significant differences between the treatment and control groups were determined using chi-square and Fisher's exact tests. MAIN RESULTS AND THE ROLE OF CHANCE:There was no effect of BPA or BPS on the proportion of bovine oocytes that reached MII (P > 0.05). BPA and BPS increased spindle abnormalities in MII oocytes at almost all concentrations tested, including those as low as 1 fM (P = 0.013) or 10 fM (P < 0.0001), respectively, compared to control. Oocytes with flattened spindles with broad poles were observed at a higher frequency at some concentrations of BPA (P = 0.0002 and P = 0.002 for 10 nM and 50 μM, respectively) or BPS (P = 0.01 for 100 nM BPS), while this spindle phenotype was absent in the controls. BPA increased chromosome misalignment at concentrations of 10 fM, 10 nM and 50 μM (P < 0.0001 to P = 0.043 depending on the dose). BPS increased chromosome misalignment at concentrations of 10 fM, 100 pM, 10 nM, 100 nM and 50 μM (P < 0.0001 to P = 0.013 depending on the dose). LIMITATIONS REASONS FOR CAUTION:Exposures to BPA or BPS were performed during the IVM of COCs to allow for determination of direct effects of these chemicals on oocyte maturation. Whole follicle culture or in vivo studies will confirm whether follicular cell interactions modify the effects of BPA or BPS on oocyte meiotic maturation. Investigation into the effects of BPA or BPS on other oocyte functions will determine whether these chemicals alter oocyte quality via mechanisms independent of the meiotic endpoints characterized here. WIDER IMPLICATIONS OF THE FINDINGS:The findings of this study show that both BPA and BPS induce spindle abnormalities and chromosome misalignment in bovine in a non-monotonic manner, and at concentrations that are orders of magnitude below those measured in humans. Taken in context with previous studies on the effects of BPA in a range of species, our data support the literature that BPA may reduce oocyte quality and lead to subsequent infertility. Additionally, these results contribute to the burgeoning field of research on BPS and suggest that BPS may indeed be a 'regrettable substitution' for BPA. STUDY FUNDING/COMPETING INTEREST(S):This study was supported by funding from the National Institutes of Health (NIH) (Grant 1R15ES024520-01). The authors declare no conflict of interest.
Bisphenol A-Induced changes in the enteric nervous system of the porcine duodenum.
Szymanska Kamila,Gonkowski Slawomir
Bisphenol A (BPA) is an organic compound from the phenolic group commonly used for the production of plastics. The use of BPA in food and drinking water containers carries a significant risk to human health since BPA can be washed out and enter consumables. BPA entering the human body with food shows a multi-directional effect and causes disorders in the functioning of many systems and organs. There is no current knowledge about the effects of BPA on the enteric nervous system. The purpose of the present study was to verify the influence of BPA on tolerable daily intake (TDI) dose (0.05 mg/kg body weight/day) and a dose ten times higher than TDI (0.5 mg/kg body weight/day) administered for 28 days on the porcine duodenum. The neurochemical characterization of the enteric neurons to five active neuronal substances was then investigated: substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT) or cocaine- and amphetamine-regulated transcript peptide (CART) with double immunofluorescence method. Both doses of BPA caused visible changes in duodenal immunoreactivity to the majority of neuronal factors studied and the obtained results show that even TDI dose may affect the living organism.
Effects of continuous bisphenol A exposure from early gestation on 90 day old rat testes function and sperm molecular profiles: A CLARITY-BPA consortium study.
Dere Edward,Anderson Linnea M,Huse Susan M,Spade Daniel J,McDonnell-Clark Elizabeth,Madnick Samantha J,Hall Susan J,Camacho Luísa,Lewis Sherry M,Vanlandingham Michelle M,Boekelheide Kim
Toxicology and applied pharmacology
Bisphenol A (BPA) is a ubiquitous industrial chemical that has been identified as an endocrine disrupting compound (EDC). There is growing concern that early life exposures to EDCs, such as BPA, can adversely affect the male reproductive tract and function. This study was conducted as part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA) to further delineate the toxicities associated with continuous exposure to BPA from early gestation, and to comprehensively examine the elicited effects on testes and sperm. NCTR Sprague Dawley rat dams were gavaged from gestational day (GD) 6 until parturition, and their pups were directly gavaged daily from postnatal day (PND) 1 to 90 with BPA (2.5, 25, 250, 2500, 25,000, 250,000 μg/kg/d) or vehicle control. At PND 90, the testes and sperm were collected for evaluation. The testes were histologically evaluated for altered germ cell apoptosis, sperm production, and altered spermiation. RNA and DNA isolated from sperm were assessed for elicited changes in global mRNA transcript abundance and altered DNA methylation. Effects of BPA were observed in changes in body, testis and epididymis weights only at the highest administered dose of BPA of 250,000 μg/kg/d. Genome-wide transcriptomic and epigenomic analyses failed to detect robust alterations in sperm mRNA and DNA methylation levels. These data indicate that prolonged exposure starting in utero to BPA over a wide range of levels has little, if any, impact on the testes and sperm molecular profiles of 90 day old rats as assessed by the histopathologic, morphometric, and molecular endpoints evaluated.
Effects of bisphenol A and its analogs bisphenol F and S on life parameters, antioxidant system, and response of defensome in the marine rotifer Brachionus koreanus.
Park Jun Chul,Lee Min-Chul,Yoon Deok-Seo,Han Jeonghoon,Kim Moonkoo,Hwang Un-Ki,Jung Jee-Hyun,Lee Jae-Seong
Aquatic toxicology (Amsterdam, Netherlands)
To understand the adverse outcome in response to bisphenol A and its analogs bisphenol F and S (BPA, BPF, and BPS), we examined acute toxicity, life parameter, and defensome in the marine rotifer Brachionus koreanus. Among the bisphenol analogs, BPA showed the highest acute toxicity and then BPF and BPS, accordingly in the view of descending magnitude of toxicity. In life parameters including life span and reproduction, BPA, BPF, and BPS were found to cause adverse effect. Both intracellular ROS level and GST activity were significantly increased (P < 0.05) in response to each dosage of bisphenol analogs exposures. In response to bisphenol analogs, defensomes of phase I, II, and III detoxification mechanism demonstrated inverse relationship between the lipophilicity of bisphenol analogs and the expression patterns of defensomes. BPA and BPF were found to have significant modulation (P < 0.05) in the expression of cytochrome P450 (CYP) and GST genes. In phase III, BPS with comparatively lower lipophilicity demonstrated highly diversified expressional pattern, suggesting that BPS is likely caused less toxicity compared to BPA and BPF. In this study, via phase I, II, and III detoxification mechanism, bisphenol A and its analogs F and S demonstrated specific detoxification mechanism in rotifer.
Mice exposed to bisphenol A exhibit depressive-like behavior with neurotransmitter and neuroactive steroid dysfunction.
Xin Frances,Fischer Erin,Krapp Christopher,Krizman Elizabeth N,Lan Yemin,Mesaros Clementina,Snyder Nathaniel W,Bansal Amita,Robinson Michael B,Simmons Rebecca A,Bartolomei Marisa S
Hormones and behavior
Fetal exposure to endocrine disrupting chemicals (EDCs) has been associated with adverse neurobehavioral outcomes across the lifespan and can persist across multiple generations of offspring. However, the underlying mechanisms driving these changes are not well understood. We investigated the molecular perturbations associated with EDC-induced behavioral changes in first (F1) and second (F2) filial generations, using the model EDC bisphenol A (BPA). C57BL/6J dams were exposed to BPA from preconception until lactation through the diet at doses (10 μg/kg bw/d-lower dose or 10 mg/kg bw/d-upper dose) representative of human exposure levels. As adults, F1 male offspring exhibited increased depressive-like behavior, measured by the forced swim test, while females were unaffected. These behavioral changes were limited to the F1 generation and were not associated with altered maternal care. Transcriptome analysis by RNA-sequencing in F1 control and upper dose BPA-exposed adult male hippocampus revealed neurotransmitter systems as major pathways disrupted by developmental BPA exposure. High performance liquid chromatography demonstrated a male-specific reduction in hippocampal serotonin. Administration of the selective serotonin reuptake inhibitor fluoxetine (20 mg/kg bw) rescued the depressive-like phenotype in males exposed to lower, but not upper, dose BPA, suggesting distinct mechanisms of action for each exposure dose. Finally, high resolution mass spectrometry revealed reduced circulating levels of the neuroactive steroid dehydroepiandrosterone in BPA-exposed males, suggesting another potential mechanism underlying the depressive-like phenotype. Thus, behavioral changes associated with early life BPA exposure may be mediated by sex-specific disruptions in the serotonergic system and/or sex steroid biogenesis in male offspring.
Impact of common environmental chemicals bisphenol A and bisphenol S on the physiology of Lumbriculus variegatus.
Vought Victoria,Wang Hong-Sheng
Environmental toxicology and pharmacology
Bisphenol A (BPA) is a component of polycarbonate plastics and a near ubiquitous environmental endocrine disrupting chemical. Bisphenol S (BPS), a substitute of BPA, is also hormonally active. This study examines the effects of aqueous exposure to BPA and BPS on the freshwater annelids Lumbriculus variegatus, a keystone species in shallow water ecosystems. Both BPA and BPS, at both low dose (10 M) and high dose (10 M), retarded the initial phase of body regrowth after cutting/fragmentation, which is the main mode of reproduction of L. variegatus. Both acute and five day exposure to BPA and BPS increased pulse rate of the dorsal blood vessel. For all the measured endpoints, the effects of BPA and BPS were nearly indistinguishable. These results indicate that BPA and BPS have similar and significant effects on the physiology of L. variegatus. These findings have implication for the potential impact of these bisphenols on invertebrates in the ecosystem.
Bisphenol-A inhibits improvement of testosterone in anxiety- and depression-like behaviors in gonadectomied male mice.
Liang Yvfeng,Li Jiahong,Jin Tao,Gu Ting,Zhu Qingjie,Hu Yizhong,Yang Yang,Li Jisui,Wu Donghong,Jiang Kesheng,Xu Xiaohong
Hormones and behavior
Bisphenol-A (BPA) is a well-known environmental endocrine disruptor. Developmental exposure to BPA affected a variety of behaviors in multiple model organisms. Our recent study found that exposure to BPA during adulthood aggravated anxiety- and depression-like states in male mice but not in females. In this study, 11-w-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.04, 0.4, or 4 mg/kg), or vehicle for 45 days. BPA (0.4 or 4 mg/kg) did not affect the elevated plus maze task of GDX mice but shortened the time on open arms and decreased the frequency of head dips of sham and TP-GDX mice. In forced swim task, BPA prolonged the total time of immobility of both sham and TP-GDX mice but not GDX mice. In addition, BPA reduced the levels of T in the serum and the brain of sham and TP-GDX mice. Western blot analysis further showed that BPA reduced the levels of androgen receptor (AR) and GABA(A)α2 receptor of the hippocampus and the amygdala in sham and inhibited the rescue of TP in these proteins levels of GDX mice. Meanwhile, BPA decreased the level of phospho-ERK1/2 in these two brain regions of sham and TP-GDX mice. These results suggest that long-term exposure to BPA inhibited TP-improved anxiety- and depression-like behaviors in GDX male mice. The down-regulated levels of GABA(A)α2 receptor and AR and an inhibited activity of ERK1/2 pathway in the hippocampus and the amygdala may be involved in these process.
Effects of Bisphenol-A on proliferation and expression of genes related to synthesis of polyamines, interferon tau and insulin-like growth factor 2 by ovine trophectoderm cells.
Elmetwally Mohammed A,Halawa Amal A,Lenis Yasser Y,Tang Wanjin,Wu Guoyao,Bazer Fuller W
Reproductive toxicology (Elmsford, N.Y.)
This study evaluated the effects of bisphenol A (BPA) on proliferation of ovine trophectoderm (oTr1) cells, as well as expression of genes for transport of arginine and synthesis of polyamines. BPA reduced proliferation of oTr1 cells at concentrations of 1 × 10, 1 × 10, 1 × 10 M compared to concentrations of 0, 1 × 10, and 1 × 10 M at 24 and 96 h of culture. Lower concentrations of BPA significantly increased expression of mRNAs for agmatinase (AGMAT), arginine decarboxylase (ADC), ornithine decarboxylase (ODC1) and solute carrier family 7 member 1 (SLC7A1). Similarly, synthesis of polyamines by oTr1 cells was greatest at lower concentrations of BPA and decreased as the dose of BPA increased. Expression of mRNAs for interferon tau (IFNT) and insulin-like growth factor 2 (IGF2) by oTr1 cells was greater than for controls at 1 × 10 M BPA. Overall, the effects of BPA on proliferation and gene expression by oTr1 cells were highly dose-dependent.
Camptothecin Efficacy to Poison Top1 Is Altered by Bisphenol A in Mouse Embryonic Fibroblasts.
Sonavane Manoj,Sykora Peter,Andrews Joel F,Sobol Robert W,Gassman Natalie R
Chemical research in toxicology
Bisphenol A (BPA) is used heavily in the production of polycarbonate plastics, thermal receipt paper, and epoxies. Ubiquitous exposure to BPA has been linked to obesity, diabetes, and breast and reproductive system cancers. Resistance to chemotherapeutic agents has also been shown in cancer cell models. Here, we investigated BPA's ability to confer resistance to camptothecin (CPT) in mouse embryonic fibroblasts (MEFs). MEFs are sensitive to CPT; however, co-exposure of BPA with CPT improved cell survival. Co-exposure significantly reduced Top1-DNA adducts, decreasing chromosomal aberrations and DNA strand break formation. This decrease occurs despite BPA treatment increasing the protein levels of Top1. By examining chromatin structure after BPA exposure, we determined that widespread compaction and loss of nuclear volume occurs. Therefore, BPA reduced CPT activity by reducing the accessibility of DNA to Top1, inhibiting DNA adduct formation, the generation of toxic DNA strand breaks, and improving cell survival.
Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis.
DeLuca Jennifer Aa,Allred Kimberly F,Menon Rani,Riordan Rebekah,Weeks Brad R,Jayaraman Arul,Allred Clinton D
Experimental biology and medicine (Maywood, N.J.)
Inflammatory bowel disease is a complex collection of disorders. Microbial dysbiosis as well as exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse. Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results. We investigated the ability of bisphenol-A to exacerbate colonic inflammation and alter microbiota metabolites derived from aromatic amino acids in an acute dextran sulfate sodium-induced colitis model. Female C57BL/6 mice were ovariectomized and exposed to bisphenol-A daily for 15 days. Disease activity measures include body weight, fecal consistency, and rectal bleeding. Colons were scored for inflammation, injury, and nodularity. Alterations in the levels of microbiota metabolites derived from aromatic amino acids known to reflect phenotypic changes in the gut microbiome were analyzed. Bisphenol-A exposure increased mortality and worsened disease activity as well as inflammation and nodularity scores in the middle colon region following dextran sulfate sodium exposure. Unique patterns of metabolites were associated with bisphenol-A consumption. Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon. This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease. Impact statement As rates of inflammatory bowel disease rise, discovery of the mechanisms related to the development of these conditions is important. Environmental exposure is hypothesized to play a role in etiology of the disease, as are alterations in the gut microbiome and the metabolites they produce. This study is the first to show that bisphenol-A alone alters tryptophan and microbiota metabolites derived from aromatic amino acids in a manner consistent with autoimmune diseases, specifically inflammatory bowel diseases, regardless of dextran sulfate sodium treatment. These findings indicate a potential mechanism by which bisphenol-A negatively affects gut physiology to exacerbate inflammation.
Hypothalamic-pituitary-ovarian axis perturbation in the basis of bisphenol A (BPA) reproductive toxicity in female zebrafish (Danio rerio).
Molina Ana,Abril Nieves,Morales-Prieto Noelia,Monterde José,Ayala Nahúm,Lora Antonio,Moyano Rosario
Ecotoxicology and environmental safety
Thousands of safety-related studies have been published on bisphenol A (BPA), an ubiquitous environmental pollutant with estrogenic activity and many other potential biological effects. In recent years, BPA exposure has been shown to cause anovulation and infertility through irreversible alteration of the hypothalamic-pituitary-gonadal axis in several organisms, including fish and mammals. Recently, the European Chemical Agency classified BPA as a "substance of very high concern" because of its endocrine-disrupting properties, which have serious effects on human health. Given the risk of exposure to BPA as a pollutant in the environment, food, and drinking water, the objective of our study was to assess the effects of this compound on the adeno-hypophysis by means of a histopathological and morphometric study of the gonadotroph cells. In addition, using quantitative real-time PCR (qRT-PCR) assays, we analyzed the changes in the expression of Cyp19b (an aromatase gene). Zebrafish were randomly distributed into five groups: a control group and 4 treated groups which were exposed to different BPA concentrations (1, 10, 100 and 1000 µg/L). The effects of the different doses on Cyp19b mRNA molecules followed a non-monotonic curve, with the 1 and 1000 µg/L doses causing dramatic decreases in the number of Cyp19b transcripts while the doses of 10 and 100 µg/L caused important increases. The consequences might be deregulation of gonadotropic hormones causing degeneration of gonadotropic cells, as observed in BPA treated animals. This is the first study in which the gonadotroph cells have been evaluated using histomorphological endpoints after BPA exposure in zebrafish.
Longitudinal Effects of Developmental Bisphenol A Exposure on Epigenome-Wide DNA Hydroxymethylation at Imprinted Loci in Mouse Blood.
Kochmanski Joseph J,Marchlewicz Elizabeth H,Cavalcante Raymond G,Perera Bambarendage P U,Sartor Maureen A,Dolinoy Dana C
Environmental health perspectives
BACKGROUND:Epigenetic machinery plays an important role in genomic imprinting, a developmental process that establishes parent-of-origin-specific monoallelic gene expression. Although a number of studies have investigated the role of 5-methylcytosine in imprinting control, the contribution of 5-hydroxymethylcytosine (5-hmC) to this epigenetic phenomenon remains unclear. OBJECTIVES:Using matched mouse blood samples (from mice at 2, 4, and 10 months of age), our objective was to examine the effects of perinatal bisphenol A (BPA) exposure (50 μg/kg diet) on longitudinal 5-hmC patterns at imprinted regions. We also aimed to test the hypothesis that 5-hmC would show defined patterns at imprinted genes that persist across the life course. METHODS:Genome-wide 5-hmC levels were measured using hydroxymethylated DNA immunoprecipitation sequencing (HMeDIP-seq). Modeling of differential hydroxymethylation by BPA exposure was performed using a pipeline of bioinformatics tools, including the R package. RESULTS:Based on BPA exposure, we identified 5,950 differentially hydroxymethylated regions (DHMRs), including 12 DHMRs that were annotated to murine imprinted genes—, , , , , , , , , , and . When visualized, these imprinted gene DHMRs showed clear, consistent patterns of differential 5-hmC by developmental BPA exposure that persisted throughout adulthood. CONCLUSIONS:These data show long-term establishment of 5-hmC marks at imprinted loci during development. Further, the effect of perinatal BPA exposure on 5-hmC at specific imprinted loci indicates that developmental exposure to environmental toxicants may alter long-term imprinted gene regulation via an epigenetic mechanism. https://doi.org/10.1289/EHP3441.
Role of Bisphenol A on the Endocannabinoid System at central and peripheral levels: Effects on adult female zebrafish.
Forner-Piquer Isabel,Santangeli Stefania,Maradonna Francesca,Verde Roberta,Piscitelli Fabiana,di Marzo Vincenzo,Habibi Hamid R,Carnevali Oliana
Bisphenol A (BPA), a widely used chemical to produce polycarbonate plastics, has become an ubiquitous pollutant due to its extensive use. Its endocrine disrupting properties have been documented in several studies, as well as its potential to induce metabolic and reproductive impairments at environmentally relevant concentrations. Recent insights highlighted the role of the Endocannabinoid System (ECS) in energy homeostasis and lipid metabolism. In fact, disruption of the ECS may induce metabolic alterations among other effects. Thus, the main objective of this study was to investigate the disruptive effects of environmentally relevant concentrations of BPA on the ECS of female zebrafish liver and brain. Adult female zebrafish were exposed for 3 weeks to three different concentrations of BPA (5 μg/L; 10 μg/L; 20 μg/L). We observed changes in the expression of a number of genes involved in the Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) metabolism in the liver and brain, as well as altered levels of endocannabinoids and endocannabinoid-like mediators. These changes were associated with greater presence of hepatic lipid vacuoles, following exposure to the highest concentration of BPA (20 μg/L) tested, although there were no changes in food intake and in the expression of the molecular markers for appetite. The overall results support the hypothesis that exposure to BPA induced changes in the central and hepatic ECS system of adult female zebrafish causing the increase of the area covered by lipids in the liver at the highest concentration tested, but not via food intake.
Evaluation of Prenatal Exposure to Bisphenol Analogues on Development and Long-Term Health of the Mammary Gland in Female Mice.
Tucker Deirdre K,Hayes Bouknight Schantel,Brar Sukhdev S,Kissling Grace E,Fenton Suzanne E
Environmental health perspectives
BACKGROUND:Continued efforts to phase out bisphenol A (BPA) from consumer products have been met with the challenges of finding safer alternatives. OBJECTIVES:This study aimed to determine whether early-life exposure to BPA and its related analogues, bisphenol AF (BPAF) and bisphenol S (BPS), could affect female pubertal mammary gland development and long-term mammary health in mice. METHODS:Timed pregnant CD-1 mice were exposed to vehicle, BPA (0.5, 5, 50 mg/kg), BPAF (0.05, 0.5, 5 mg/kg), or BPS (0.05, 0.5, 5 mg/kg) via oral gavage between gestation days 10–17. Mammary glands were collected from resulting female offspring at postnatal day (PND) 20, 28, 35, and 56, and at 3, 8, and 14 months for whole mount, histopathological evaluation, and quantitative real-time polymerase chain reaction (qPCR); serum steroid concentrations were also measured at these time points. RESULTS:In the bisphenol-exposed mice, accelerated mammary gland development was evident during early puberty and persisted into adulthood. By late adulthood, mammary glands from bisphenol-exposed female offspring exhibited adverse morphology in comparison with controls; most prominent were undifferentiated duct ends, significantly more lobuloalveolar hyperplasia and perivascular inflammation, and various tumors, including adenocarcinomas. Effects were especially prominent in the BPAF 5 mg/kg and BPS 0.5 mg/kg groups. Serum steroid concentrations and mammary mRNA levels of , , , and were similar to controls. CONCLUSIONS:These data demonstrate that prenatal exposure of mice to BPAF or BPS induced precocious development of the mammary gland, and that siblings were significantly more susceptible to spontaneous preneoplastic epithelial lesions and inflammation, with an incidence greater than that observed in vehicle- and BPA-exposed animals. https://doi.org/10.1289/EHP3189.
Bisphenol A and microglia: could microglia be responsive to this environmental contaminant during neural development?
Rosin Jessica M,Kurrasch Deborah M
American journal of physiology. Endocrinology and metabolism
There is a growing interest in the functional role of microglia in the developing brain. In our laboratory, we have become particularly intrigued as to whether fetal microglia in the embryonic brain are susceptible to maternal challenges in utero (e.g., maternal infection, stress) and, if so, whether their precocious activation could then adversely influence brain development. One such challenge that is newly arising in this field is whether microglia might be downstream targets to endocrine-disrupting chemicals, such as the plasticizer bisphenol A (BPA), which functions in part by mimicking estrogen structure and function. A growing body of evidence demonstrates that gestational exposure to BPA has adverse effects on brain development, although the exact mechanisms are still emerging. Given that microglia express estrogen receptors and steroid-producing enzymes, microglia might be an unappreciated target of BPA. Mechanistically, we propose that BPA binding to estrogen receptors within microglia initiates transcription of downstream target genes, which then leads to activation of microglia that can then perhaps adversely influence brain development. Here, we first briefly outline the current understanding of how microglia may influence brain development and then describe how this literature overlaps with our understanding of BPA's effects during similar time points. We also outline the current literature demonstrating that BPA exposure affects microglia. We conclude by discussing our thoughts on the mechanisms through which exposure to BPA could disrupt normal microglia functions, ultimately affecting brain development that could potentially lead to lasting behavioral effects and perhaps even neuroendocrine diseases such as obesity.
Histological investigations on thymus of male rats prenatally exposed to bisphenol A.
Aydemir Işıl,Kum Şadiye,Tuğlu Mehmet İbrahim
Bisphenol A is called as a endocrine-distrupting chemical because of the its steroid-like activity and it used in the construction of plastic containing materials. It is indicated that bisphenol A can pass the human serum, urine, follicular fluid, placenta and umblical cord as a result of the use of substances containing this agent. In this study, we aimed to investigate the effects of bisphenol A on the development of the thymus, a primary lymphoid organ which plays an important role in the specific immunity. The adult pregnant female rats were administered orally with bisphenol A (for 21 days) and postnatal thymus samples were obtained on day 21, 45 and 90 and were performed for histochemical and immunohistochemical staining for CD3, CD4, CD8 and CD79a and TUNEL assay for the apoptotic cells. Evaluation of all groups, CD3, CD4, CD8 and CD79a stainings were decreased in the experimental groups compared with control group. The apoptotic cells were determined in the all groups on day 90 as a result of the thymus involution. It is noted that there was not any histological and morphological damages in the rats prenatally exposed the bisphenol A. The effect of the bisphenol A is unknown in the future, but there is no problem in the adult rats.
Effects of diethylene glycol dibenzoate and Bisphenol A on the lipid metabolism of Danio rerio.
Santangeli Stefania,Notarstefano Valentina,Maradonna Francesca,Giorgini Elisabetta,Gioacchini Giorgia,Forner-Piquer Isabel,Habibi Hamid R,Carnevali Oliana
The Science of the total environment
Endocrine disrupting chemicals (EDCs) are known to disrupt normal metabolism and can influence the incidence of obesity in animals and humans. EDCs can exert adverse effects at low concentrations, often in a non-monotonic dose-related fashion. Among EDCs, Bisphenol A (BPA) is extensively used in the production of polycarbonate plastic, and is among the most abundant contaminants in the world. Diethylene glycol dibenzoate (DGB), an approved alternative to phthalates in the production of plastic and latex products, however, is less abundant and its effects are almost completely unknown. The aim of this study is to provide information on the hepatic effects of BPA and DGB on lipid metabolism, and investigate possible links between these contaminants and the increased incidence of obesity. In the present study, we exposed zebrafish to three different BPA doses (5; 10; 20 μg/L) and five different doses of DGB (0.01; 0.1; 1; 10; 100 μg/L) for a period of 21 days, and investigated transcript levels for genes involved in lipid metabolism as well as measuring liver content of phosphates, lipids and proteins. The results demonstrate disruptive effects of BPA and DGB on lipid metabolism in a non-monotonic dose-related fashion. The lowest dose of BPA increased the storage of triglycerides and promoted fatty acid synthesis, while the highest concentration promoted de novo lipogenesis and cholesterologenesis. Exposure to DGB was also found to affect lipid metabolism leading to increased lipid production and mobilization in a non-monotonic dose-related fashion. Analysis of BPA and DGB by FT-IR revealed that exposure to both compounds lead to changes in the biochemical composition of liver. The findings provide a support for the hypothesis that BPA and DGB may be among the environmental contaminants with obesogenic property.
Bisphenol A induced male germ cell apoptosis via IFNβ-XAF1-XIAP pathway in adult mice.
Jiang Xiao,Yin Li,Zhang Ning,Han Fei,Liu Wen-Bin,Zhang Xi,Chen Hong-Qiang,Cao Jia,Liu Jin-Yi
Toxicology and applied pharmacology
Bisphenol A (BPA) impairs male fertility by acting as an endocrine disruptor. However, the mechanisms by which BPA cause reproductive toxicity are not fully elucidated. Here, we explored the role of XAF1, a novel pro-apoptosis molecule, in BPA-induced abnormal spermatogenesis and the transcriptional regulation mechanism of BPA-induced XAF1. BPA exposure detrimentally impacted spermatogenesis by inducing excessive germ cell apoptosis. XAF1 was upregulated in germ cells after BPA exposure, which was involved in the apoptosis pathway. In addition, the expression levels of XIAP and XAF1 were inversely correlated after BPA exposure. Knockdown of XAF1 expression partially inhibited the apoptosis of GC-2 cells, suppressed the activation of caspase 3 and improved the BPA-induced XIAP expression. Moreover, IFNβ expression levels were significantly upregulated after BPA exposure both in vitro and in vivo, and these levels were positively related to the expression of XAF1. Furthermore, IFNβ knockdown reduced the expression of XAF1 and increased the expression of XIAP in BPA-treated GC-2 cells. Together, these data indicated that BPA triggers male germ cell apoptosis in mice via the IFNβ-XAF1-XIAP pathway, which may contribute to BPA-induced testis toxicity.
The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus.
International journal of molecular sciences
Bisphenol A (BPA), a substance commonly used in the manufacture of plastics, shows multidirectional negative effects on humans and animals. Due to similarities to estrogens, BPA initially leads to disorders in the reproductive system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active substance which enhances the survivability of cells, inhibits apoptosis, and protects tissues against damaging factors. Because the influence of BPA on the nervous system has also been described, the aim of the present study was to investigate for the first time the influence of various doses of BPA on neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus using the routine single- and double-immunofluorescence technique. The obtained results have shown that BPA increases the number and affects the neurochemical characterization of NRG-1-LI in the uterus, and changes are visible even under the impact of small doses of this toxin. The character of observed changes depended on the dose of BPA and the part of the uterus studied. These observations suggest that NRG-1 in nerves supplying the uterus may play roles in adaptive and protective mechanisms under the impact of BPA.