The Effect of Nanoparticles of Zinc Oxide, Nickel Oxide, or Their Mixture on Rat Testes: A Time‐Dependent Study

Zinc oxide nanoparticles (ZnO-NPs) and nickel oxide nanoparticles (NiO-NPs) have recently been associated with potential adverse effects on human health following their increased application in consumer products. While previous studies have focused on hepatorenal and pulmonary toxicities, their effects on male reproduction remain inconclusive. This study aimed to assess the individual and combined effects of these NPs on testicular structure and function in male Sprague-Dawley rats, at different time points. Thirty-six male rats were divided into four groups and treated intraperitoneally with either normal saline, ZnO-NPs (200 mg/kg), NiO-NPs (50 mg/kg), or their combination. Testosterone levels, oxidative stress markers, histomorphometric changes, and spermatogenesis grading were assessed at 7, 14, and 21 days post-exposure. Our results revealed that both NPs significantly decreased testosterone levels and depleted the antioxidant system while increasing lipid peroxidation. Additionally, impaired spermatogenesis was observed, accompanied by testicular histological and morphometric alterations. Notably, the toxicity was time dependent: NiO-NPs exerted a progressive toxic effect, while ZnO-NPs showed early recovery. Interestingly, co-exposed NPs initially showed minimal reproductive damage but developed enhanced toxicity at the final time point. To conclude, acute exposure to these NPs exerts different time-dependent patterns of reproductive toxicity in male rats. Co-exposure initially provided protection that shifted to enhanced toxicity, suggesting the involvement of ionic interactions between NPs in modulating their combined effect.