Zinc oxide nanoparticle causes toxicity to the development of mouse oocyte and early embryo

• Published in: Toxicology letters Vol. 358; pp. 48 - 58
• Main Authors: Huang, Chunjie, Wu, Di, Khan, Faheem Ahmed, Wang, Yongsheng, Xu, Junjie, Luo, Chunhai, Zhang, Kejia, Sun, Fei, Huo, Lijun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022
• Subjects: Animals; Autophagy and apoptosis; Cytoskeleton; Environmental perturbation; Grp78; Mammals; Mice; Mitochondria; Nanoparticles - toxicity; Oocytes; Oxidative Stress; Zinc Oxide - metabolism; Autophagy and apoptosis; Grp78; Oxidative stress; Cytoskeleton; Environmental perturbation
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2022.01.010

[Display omitted] •ZnO nanoparticle causes developmental arrest of mouse oocyte and embryo.•ZnO nanoparticle incites organelle stress and cytoskeleton disorganization in oocytes.•Intervening neither apoptosis nor autophagy subverts oocyte death fate.•Grp78 depletion recapitulates ZnO NP-induced defective spindle assembly.•Compared to oocytes, embryos are extremely sensitive to ZnO NP. Zinc oxide nanoparticle (ZnO NP) is one of the most widely used nanomaterial in industrial and commercial products. Here, we reported hazardous effects of ZnO NP on the development of mouse oocyte and pre-implantation embryo. ZnO NP compromises meiosis partially by induction of oxidative stress as antioxidant rescues the development of ZnO NP-exposed oocytes, albeit with limited efficiency. It causes mitochondrial- and endoplasmic reticulum stresss which thereby activates autophagy and apoptosis to trigger oocyte demise. Examining ZnO NP-exposed oocytes that complete M-phase entry witnesses a disruption in meiotic cytoskeleton architecture. Intriguingly, loss of Grp78, a chaperone in the ER, phenocopies ZnO NP-induced meiotic defects and cytoskeleton disorganization. Importantly however, ZnO NP commences cytotoxicity by more than releasing of Zn2+ in that ZnCl2 to a much less extent recapitulates ZnO NP-induced phenomena. The prevailing DNA damage is another causative to developmental arrest and degeneration of oocytes and early embryos, but compared with oocytes, embryos are more sensitive to ZnO NP and succumb to death. ZnO NP is demonstrated in this study to be toxic for oocytes and enbryos in mammals, which warrants careful evaluation of human exposure with regard to its influence on reproductive health.