ZnO nanoparticles enhanced germ cell apoptosis in Caenorhabditis elegans , in comparison with ZnCl ₂

Abstract

Effects of ZnO NPs and ionic Zn on germline apoptosis and the regulation of genes in the apoptosis pathway were investigated in vivo using the model organism Caenorhabditis elegans.Age synchronized Bristol N2 worms were exposed to ZnO NPs and ZnCl 2 at concentrations of 6.14 Â 10 À1, 61.4, and 614 lM form larval stage 1 (L1) to early adulthood. Possible ZnO nanoparticles were observed under the worm cuticle and also in the gonadal region by transmission electron microscopy (TEM). ZnO NPs and ZnCl 2 both significantly increased the number of apoptotic cells as compared with controls in the 61.4 and 614 lM treatment groups (P < .05). However, ZnO NPs induced more apoptotic cells in the 61.4 lM treatment than ZnCl 2 (P < .05), suggesting ZnO NP is more potent in inducing apoptosis at specific exposure concentration. Findings using the MD701 (bcIs39 [(lim-7)ced-1p::GFP þ lin-15(þ)]) strain further confirmed the observations in N2 strain. Genes involved in the apoptosis pathway (ced-13, ced-3, ced-4, ced-9, cep-1, dpl-1, efl-1, efl-2, egl-1, egl-38, lin-35, pax-2, and sir-2.1) were in general upregulated in response to ZnO NP exposure. The cep-1/p53 gene was up-regulated in gene expression assay. In the cep-1 loss of function mutant, no significant increase in apoptosis was observed. Therefore, the increased apoptosis resulting from ZnO NPs exposure is likely cep-1/p53 dependent. This study provides evidence that ZnO nanoparticles affect germ cell apoptotic machinery as a potential mechanism of reproductive toxicity.

Exposure to Zinc oxide nanoparticles during pregnancy induces oocyte DNA damage and affects ovarian reserve of mouse offspring

“…12.5 dpc fetal ovaries were isolated and cultured with nZnO in vitro , and nZnO penetrated into the fetal ovaries and caused cytotoxicity to the germ cells. Consistent with previous studies [ 7 , 31 – 33 ], Exposure to nZnO mainly induced cellular DNA damage and as a consequence resulted in increased expression of apoptosis related proteins in the fetal ovaries. Since several types of cells exist within the fetal ovaries, we next investigated whether the nZnO penetrated and affected particular cell types.…”

The Impact of Zinc Oxide Nanoparticles on Male (In)Fertility

“…Exposure of C. elegans to ZnO NPs caused an increase in the apoptotic cell number, resulting from a change in apoptotic gene regulation. The apoptotic genes cep-1, cep-13, efl-2, egl-1, lin-35, and sir-2.1 were significantly upregulated in the presence of ZnO NPs, promoting cell apoptosis [79]. Although it is necessary to be aware that this animal model is hermaphrodite, in this study, no distinction was made between germ cells.…”

Different Strategies to Attenuate the Toxic Effects of Zinc Oxide Nanoparticles on Spermatogonia Cells

“…They can easily start a cascade of chain reactions, leading to oxidative stress, which can seriously alter cell membranes and structures [ 21 ]. Several in vitro and in vivo studies have demonstrated that ZnO NPs induce substantial cytotoxicity, mainly through the overproduction of ROS [ 3 , 22 , 23 , 24 , 25 ]. We might speculate that the increase in ROS is normally accompanied by an increase in DNA damage and consequently, increased genotoxicity.…”