PDF(Pubmed)
Abstract：
The implementation of Zinc oxide nanoparticles (ZnO NPs) raises concerns regarding their potential toxic effects on human health. Although more and more researches have confirmed the toxic effects of ZnO NPs, limited attention has been given to their impact on the early embryonic nervous system. This study aimed to explore the impact of exposure to ZnO NPs on early neurogenesis and explore its underlying mechanisms. We conducted experiments here to confirm the hypothesis that exposure to ZnO NPs causes neural tube defects in early embryonic development. We first used mouse and chicken embryos to confirm that ZnO NPs and the Zn2+ they release are able to penetrate the placental barrier, influence fetal growth and result in incomplete neural tube closure. Using SH-SY5Y cells, we determined that ZnO NPs-induced incomplete neural tube closure was caused by activation of various cell death modes, including ferroptosis, apoptosis and autophagy. Moreover, dissolved Zn2+ played a role in triggering widespread cell death. ZnO NPs were accumulated within mitochondria after entering cells, damaging mitochondrial function and resulting in the over production of reactive oxygen species, ultimately inducing cellular oxidative stress. The N-acetylcysteine (NAC) exhibits significant efficacy in mitigating cellular oxidative stress, thereby alleviating the cytotoxicity and neurotoxicity brought about by ZnO NPs. These findings indicated that the exposure of ZnO NPs in early embryonic development can induce cell death through oxidative stress, resulting in a reduced number of cells involved in early neural tube closure and ultimately resulting in incomplete neural tube closure during embryo development. The findings of this study could raise public awareness regarding the potential risks associated with the exposure and use of ZnO NPs in early pregnancy.
摘要：
氧化锌纳米颗粒（ZnONPs）的实施引起了人们对其对人类健康的潜在毒性影响的担忧。虽然越来越多的研究证实了ZnONPs的毒性作用,它们对早期胚胎神经系统的影响受到了有限的关注。本研究旨在探讨ZnONPs对早期神经发生的影响及其潜在机制。我们在这里进行了实验，以证实以下假设：暴露于ZnONPs会导致早期胚胎发育中的神经管缺陷。我们首先使用小鼠和鸡的胚胎来证实ZnONPs和它们释放的Zn2+能够穿透胎盘屏障,影响胎儿生长并导致神经管闭合不全。使用SH-SY5Y单元格，我们确定ZnONPs诱导的不完全神经管闭合是由各种细胞死亡模式的激活引起的，包括铁性凋亡,细胞凋亡和自噬。此外，溶解的Zn2+在引发广泛的细胞死亡中起作用。ZnONPs进入细胞后在线粒体内积累，破坏线粒体功能并导致活性氧的过度产生，最终诱导细胞氧化应激。N-乙酰半胱氨酸（NAC）在减轻细胞氧化应激方面具有显着的功效，从而减轻ZnONP带来的细胞毒性和神经毒性。这些发现表明，在胚胎发育早期暴露ZnONPs可以通过氧化应激诱导细胞死亡，导致参与早期神经管闭合的细胞数量减少，最终导致胚胎发育过程中神经管闭合不完全。这项研究的结果可以提高公众对与怀孕早期接触和使用ZnONPs相关的潜在风险的认识。
