Introduction Zinc oxide nanoparticles (ZnO NPs) participate in all aspects of our lives, but with their wide application, more and more disadvantages are exposed. The goal of this study was to investigate the toxicity of ZnO NPs in female mice ovaries and explore its potential mechanism. Methods In this study, adult female mice were orally exposed to 0, 100, 200, and 400 mg/kg ZnO NPs for 7 days. We explored the underlying mechanisms via the intraperitoneal injection of N-acetyl-cysteine (NAC), an inhibitor of oxidative stress, and salubrinal (Sal), an inhibitor of endoplasmic reticulum (ER) stress. Results The results indicated that serum estradiol and progesterone levels declined greatly with increasing ZnO NPs dosage. Hematoxylin and eosin (HE) staining revealed increased atretic follicles and exfoliated follicular granulosa cells. Moreover, at the transcriptional level, antioxidant-related genes such as Keap1 and Nrf2 , and ER stress-related genes PERK, eIF2α , and ATF4 were markedly upregulated. In addition, the expression of Caspase12, Caspase9 , and Caspase3 , which are genes related to apoptosis, was also upregulated in all ZnO NPs treatment groups. Serum malondialdehyde (MDA) content was remarkably up-regulated, whereas superoxide dismutase (SOD) activity was down-regulated. The 400 mg/kg ZnO NPs treatment group suffered the most substantial harm. However, ovarian damage was repaired when NAC and Sal were added to this group. Conclusion ZnO NPs had toxic effects on the ovary of female mice, which were due to oxidative stress, ER stress, and the eventual activation of apoptosis.

Numerous reports confirm that microplastics exposure could induce reproductive toxicity in mammals. However, the effects of microplastics exposure during juveniles on ovarian apoptosis through oxidative and endoplasmic reticulum (ER) stresses remains unclear, which is the focus of our study. In the present study, female rats (4 weeks old) were exposed to polystyrene microplastics (PS-MPs, 1 μm) at different dosages (0, 0.5, and 2.0 mg/kg) for 28 days. Findings revealed that 2.0 mg/kg of PS-MPs distinctly increased the atretic follicle ratio in the ovary and dramatically reduced the serum levels of estrogen and progesterone. Additionally, the oxidative stress indicators declined, including the activity of superoxide dismutase and catalase, whereas the malondialdehyde content in the ovary was considerably enhanced in the 2.0 mg/kg PS-MPs group. Furthermore, the expressions of genes related to ER stress (PERK, eIF2α, ATF4, and CHOP) and apoptosis were remarkably elevated in the 2.0 mg/kg PS-MPs group compared with those in the control group. We found that PS-MPs induced oxidative stress and activated the PERK-eIF2α-ATF4-CHOP signaling pathway in juvenile rats. Moreover, with the oxidative stress inhibitor N-acetyl-cysteine and eIF2α dephosphorylation blocker Salubrinal treatment, ovarian damage induced by PS-MPs was repaired and associated enzyme activities were improved. Overall, our results indicated that PS-MPs exposure induced ovarian injury associated with oxidative stress and activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in juvenile rats, providing new prospects for assessing the health risks of children exposed to microplastics.