Zinc oxide nanoparticles exposure-induced oxidative stress restricts cranial neural crest development during chicken embryogenesis.
Yan Yu,Wang Guang,Huang Ju,Zhang Yan,Cheng Xin,Chuai Manli,Brand-Saberi Beate,Chen Guobing,Jiang Xiaohua,Yang Xuesong
Ecotoxicology and environmental safety
Zinc oxide Nanoparticles (ZnO NPs) are widely used as emerging materials in agricultural and food-related fields, which exists potential safety hazards to public health and environment while bringing an added level of convenience to our original life. It has been proved that ZnO NPs could be taken up by pregnant women and passed through human placental barrier. However, the toxic potential for embryo development remains largely unanswered. In this study, we discovered that ZnO NPs caused the cytotoxicity in vitro. Inhibition of free Zn ions in solution by EDTA or inhibition of Zn ions absorption by CaCl could partially eliminate ZnO NPs-mediated cell toxicity, though not redeem completely. This indicated that both nanoparticles and the release of Zn ions were involved in ZnO NPs-mediated cytotoxicity. In addition, we also found that both nanoparticles and Zn ion release triggered reactive oxygen species (ROS) production, which further induced cell toxicity, inflammation and apoptosis, which are mediated by NF-κB signaling cascades and the mitochondria dysfunction, respectively. Eventually, these events lead to the suppressed production and migration of cranial neural crest cells (CNCCs), which subsequently prompts the craniofacial defects in chicken embryos. The application of the antioxidant N-Acetyl-L-cysteine (NAC) rescued the ZnO NPs-induced cell toxicity and malformation of the CNCCs, which further verified our hypothesis. Our results revealed the relevant mechanism of ZnO NPs exposure-inhibited the development of CNCCs, which absolutely contribute to assess the risk of nanoparticles application.
10.1016/j.ecoenv.2020.110415
Protective effect of the NAC and Sal on zinc oxide nanoparticles-induced reproductive and development toxicity in pregnant mice.
Chen Bolu,Hong Wuding,Tang Yizhou,Zhao Yu,Aguilar Zoraida P,Xu Hengyi
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
The growing use of zinc oxide nanoparticles (ZnO NPs) in various applications has raised many concerns about the potential risks to human health. In this research, the protective effects of cellular oxidative stress inhibitor N-Acetyl-cysteine (NAC) and endoplasmic reticulum (ER) stress inhibitor Salubrinal (Sal) on reproductive toxicity induced by ZnO NPs were investigated. The results showed that application of these two kinds of cell stress inhibitors after oral ingestion of ZnO NPs could prevent the weight loss of pregnant mice; reduce zinc content in the uterus, placenta and fetus; reduce abnormal development of the offspring; and decrease fetal abortion. Furthermore, RT-qPCR, Western blot and immunofluorescence assay results indicated that NAC restored the expression of Gclc, reduced the expression of ATF4, JNK and Caspase-12, and decreased the expression of eNOS and IGF-1, in the placenta. Sal decreased the expression of ATF4, JNK and Caspase-12, and increased the expression of eNOS and IGF-1caused by the oral ingestion of ZnO NPs. These results indicated that treatment with NAC and Sal after oral exposure could reduce reproductive and development toxicity caused by ZnO NPs which induced reproductive and development toxicity that was probably caused by the activation of oxide stress and ER stress.
10.1016/j.fct.2020.111552
Exposure to Zinc oxide nanoparticles during pregnancy induces oocyte DNA damage and affects ovarian reserve of mouse offspring.
Zhai Qiu-Yue,Ge Wei,Wang Jun-Jie,Sun Xiao-Feng,Ma Jin-Mei,Liu Jing-Cai,Zhao Yong,Feng Yan-Zhong,Dyce Paul W,De Felici Massimo,Shen Wei
Aging
Zinc oxide nanoparticles (nZnO) have been shown to have higher toxic effects likely due to their ion-shedding ability and low solubility under neutral conditions. In order to investigate whether exposure to nZnO during embryonic development affects ovary development, 12.5 day post coitum (dpc) fetal mouse ovaries were cultured in the presence of nZnO for 6 days. We found that the nanoparticles (NPs) accumulated within the oocyte cytoplasm in a dose dependent manner, caused DNA damage and apoptosis, and result in a significant decrease in oocyte numbers. No such effects were observed when the ovaries were incubated in the presence of ZnSO or bulk ZnO as controls. In addition, we injected intravenously 16 mg/kg body weight nZnO in 12.5 dpc pregnant mice on two consecutive days and analyzed the ovaries of fetuses or offspring at three critical periods of oogenesis: 17.5 dpc, 3 days post-partum (dpp) and 21 dpp. Evidence of increased DNA damage in pachytene oocytes in fetal ovaries and impaired primordial follicle assembly and folliculogenesis dynamics in the ovaries of the offspring were found. Our results indicate that certain types of NPs affect pre- and post-natal oogenesis and .
10.18632/aging.101539
Nano Zinc Oxide Induced Fetal Mice Growth Restriction, Based on Oxide Stress and Endoplasmic Reticulum Stress.
Chen Bolu,Hong Wuding,Yang Pengfei,Tang Yizhou,Zhao Yu,Aguilar Zoraida P,Xu Hengyi
Nanomaterials (Basel, Switzerland)
ZnO NPs have been assessed to show adverse effects on reproductive organs, but the molecular mechanisms of reproductive toxicity have not been sufficiently studied. In this research, the dosage effects from the oral exposure of ZnO NPs (30 nm) to pregnant mice in gestation day 10.5 to 17.5 was analyzed. Pregnant mice exposed to ZnO NPs induced dam injury, mice fetal growth restriction, and the fetus number decreased. The pathological evaluation showed that ZnO NPs exposure caused placental spongiotrophoblast area decease and structural damage. The RT-qPCR and immunocytochemistry data indicated that ZnO NPs could induce placenta oxide stress, endoplasmic reticulum stress responses, apoptosis, and altered placental function. These findings indicated that ZnO NPs could induce dam injury and fetal growth restriction. Reproductive toxicity of ZnO NPs may be due to placental injury and function alteration caused by apoptosis, oxide stress, and endoplasmic reticulum stress after ZnO NPs exposure.
10.3390/nano10020259
Prenatal exposure to nanosized zinc oxide in rats: neurotoxicity and postnatal impaired learning and memory ability.
Xiaoli Feng,Junrong Wu,Xuan Lai,Yanli Zhang,Limin Wei,Jia Liu,Longquan Shao
Nanomedicine (London, England)
AIM:To examine the neurotoxicity of prenatal exposure to ZnO nanoparticles on rat offspring. MATERIALS & METHODS:Pregnant Sprague-Dawley rats were exposed to ZnO nanoparticles (NPs) by gavage. Toxicity was assessed including zinc biodistribution, cerebral histopathology, antioxidant status and learning and memory capability. RESULTS:A significantly elevated concentration of zinc was detected in offspring brains. Transmission electron microscope observations showed abnormal neuron ultrastructures. Histopathologic changes such as decreased proliferation and higher apoptotic death were observed. An obvious imbalanced antioxidant status occurred in brains. Adult experimental offspring exhibited impaired learning and memory behavior in the Morris water maze test compared with control groups. CONCLUSION:These adverse effects on offspring brain may cause impaired learning and memory capabilities in adulthood, particularly in female rats.
10.2217/nnm-2016-0397
Prenatal development toxicity study of zinc oxide nanoparticles in rats.
Hong Jeong-Sup,Park Myeong-Kyu,Kim Min-Seok,Lim Jeong-Hyeon,Park Gil-Jong,Maeng Eun-Ho,Shin Jae-Ho,Kim Meyoung-Kon,Jeong Jayoung,Park Jin-A,Kim Jong-Choon,Shin Ho-Chul
International journal of nanomedicine
This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnO(SM20(+)) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo-fetal development after maternal exposure over the period of gestational days 5-19 with Sprague-Dawley rats. ZnO(SM20(+)) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnO(SM20(+)) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group.
10.2147/IJN.S57932
Oral Co-Exposures to zinc oxide nanoparticles and CdCl induced maternal-fetal pollutant transfer and embryotoxicity by damaging placental barriers.
Teng Chuanfeng,Jia Jianbo,Wang Zhiping,Yan Bing
Ecotoxicology and environmental safety
Synergistic toxicity from multiple environmental pollutants poses greater threat to humans, especially to susceptible pregnant population. Here we evaluated combined toxicity from environment pollutants zinc oxide nanoparticles (ZnO NPs) and cadmium chloride (CdCl) using two pregnant mice models established by oral administration during peri-implantation or organogenesis period. We found that exposures to combined pollutants only at organogenesis stage induced higher fetal deformity rate compared to co-exposures at peri-implantation stage. We further discovered that surface charge of ZnO NPs were modified after Cd adsorption and the resulting nanoadducts caused more severe damages in placental barriers by causing shed endothelial cells and decreased expressions of tight junction proteins ZO1, occludin, claudin-4 and claudin-8. These cellular and molecular events enhanced maternal-fetal transfer of both pollutants and aggravated embryotoxicity. Our findings help elucidate synergistic embryotoxicity by nanoparticle/pollutant adducts and establish proper safety criteria for pregnant population in an era that nanotechnology-based products are widely used.
10.1016/j.ecoenv.2019.109956
Effect of zinc oxide nanoparticles on dams and embryo-fetal development in rats.
Hong Jeong-Sup,Park Myeong-Kyu,Kim Min-Seok,Lim Jeong-Hyeon,Park Gil-Jong,Maeng Eun-Ho,Shin Jae-Ho,Kim Yu-Ri,Kim Meyoung-Kon,Lee Jong-Kwon,Park Jin-A,Kim Jong-Choon,Shin Ho-Chul
International journal of nanomedicine
This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnO(SM20[-]) NPs; negatively charged, 20 nm) on pregnant dams and embryo-fetal development after maternal exposure over the period of gestational days 5-19 with Sprague Dawley rats. ZnO(SM20(-)) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnO(SM20(-)) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day.
10.2147/IJN.S57931
Size-dependent maternal-fetal transfer and fetal developmental toxicity of ZnO nanoparticles after oral exposures in pregnant mice.
Teng Chuanfeng,Jia Jianbo,Wang Zhiping,Sharma Virender K,Yan Bing
Ecotoxicology and environmental safety
The widespread application of nanomaterial-based products has caused safety concerns worldwide, especially for susceptible pregnant population. Here, we revealed the effect of the size of ZnO nanoparticles (ZnO NPs) on placental and fetal developmental toxicities. We found that smaller ZnO NPs (13 nm) were able to cross both the intestinal barrier and the placental barrier to reach the fetus after oral exposure and caused fetal developmental toxicity. However, larger ZnO NPs (57 nm) and bulk ZnO particles were not able to cross these barriers and exert effects. We also discovered that the organogenesis period (GD7-GD16) was more vulnerable to such toxicity compared with the peri-implantation period (GD1-GD10) of pregnancy. This new understanding that smaller nanoparticles may pass through multiple biological barriers to induce toxicity in susceptible populations is crucial for the safeguarding of humans from the widespread application of nanoproducts. The discovery that the organogenesis stage in pregnancy is more vulnerable to nanotoxicity than the peri-implantation stage is provides valuable guidance for an improved protection strategy.
10.1016/j.ecoenv.2019.109439