Journal
ENVIRONMENT INTERNATIONAL
Volume 152, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.envint.2021.106495
Keywords
Zinc oxide nanoparticles; Neural tube defect; Endoplasmic reticulum stress; Ca2+; Embryogenesis
Categories
Funding
- NSFC [31971108, 31771331]
- Natural Science Foundation of Guangdong Province [2020A1515010209]
- Science and Technology Planning Project of Guangdong Province [2017A050506029, 2016B030229002]
- Special Funds for the Cultivation of Guangdong College Students' Scientific and Technological Innovation [pdjh2020a0063]
- Students Research Training Program Fund [201910559090]
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Exposure to ZnO NPs may lead to developmental neural cell death, resulting in failure of neural tube closure and ultimately neural tube defects. Endoplasmic reticulum stress and increased intracellular calcium concentration may be key mechanisms in the neurotoxicity induced by ZnO NPs.
Zinc oxide nanoparticles (ZnO NPs) have been increasingly and widely utilized in various fields, such as agriculture, food and cosmetics. However, various levels of adverse impacts of ZnO NPs on the ecological environment and public health have been associated with each stage of their production, use and disposal. ZnO NPs can be ingested by pregnant women and transferred to developing embryos/foetus through the placental barrier, however, the potential toxicity of ZnO NPs to embryonic and foetal development is largely unclear. In this study, we discovered that ZnO NPs exposure caused growth proportional failure of neural tube closure in mouse and chicken embryos and a simultaneous increase in apoptosis in the developing neural tubes of chicken embryos, which was verified in an in vitro experiment using the SH-SY5Y cell line. Furthermore, removal of free Zn2+ ions with EDTA or inhibition of Zn2+ ion absorption by CaCl2 partially alleviated the neurotoxicity induced by ZnO NPs, implying that ZnO NPs-induced developmental neurotoxicity is probably due to both ZnO NPs and the Zn2+ ions released from ZnO NPs. In addition, we found that ZnO NPs exposure caused endoplasmic reticulum stressmediated apoptosis driven mainly by an increase in intracellular calcium (Ca2+) concentrations, rather than by the activation of three membrane protein receptors (ATF6, IRE-1 and PERK). Thus, Ca2+ imbalance-mediated apoptosis in the context of ZnO NPs exposure may lead to cellular dysfunctions in developing neural precursors, such as, abnormalities involved in neural tube closure, ultimately leading to neural tube defects (NTDs) during embryogenesis. In sum, our results revealed that ZnO NPs exposure greatly increases the risk of failure of neural tube closure through endoplasmic reticulum stress-mediated neural cell death in the developing embryos, which may further lead to the NTD in fetal stage, including failure of neural tube closure.
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