Background: Despite the beneficial effects of zinc oxide nanoparticles (ZnONPs) on different biomedical applications, including their antioxidant and anti-inflammatory ones, it might have cytotoxic and genotoxic impacts on the male reproductive system. Objective: The current study compares the effect of zinc oxide nanoparticles and their bulk form, at different doses, on male rats' reproductive performance, testicular antioxidants, gene expression, and histopathology. Materials and Methods: Thirty male rats were randomly allocated equally in five groups. The control one was injected with Tween 80 (10%). The zinc oxide nanoparticle (ZnONP) groups received ZnONPs < 50 nm, specifically, 5 mg/kg (ZnONP-1) and 10 mg/kg (ZnONP-2). The bulk zinc oxide (BZnO) groups were administered 5 mg/kg (BZnO-1) and 10 mg/kg (BZnO-2), correspondingly. Rats were injected intraperitoneally with the respected materials, twice/week for eight consecutive weeks. Finally, the male rats' sexual behavior and their pup's performance were determined in a monogamous mating system. Rats were then anesthetized and sacrificed for semen characteristics evaluation and tissue collection for antioxidant and hormones analysis, gene expression, and histopathological examination. Results: It was shown that ZnONP-1 improved sexual behavior, semen characteristics, and pup's performance compared to its bulk form. Similarly, the testicular antioxidants activity, glutathione (GSH), and superoxide dismutase (SOD) increased with a decrease in the malonaldehyde (MDA), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. It also improves the reproductive hormone levels and mRNA expression of different steroidogenesis-associated genes and anti-apoptotic genes. Conclusion: It can be concluded that zinc oxide nanoparticles, administered at 5 mg/kg, had the most beneficial effect on male reproductive performance, while 10 mg/kg could have a detrimental effect.
Keywords: antioxidant; bulk; semen; sexual behavior; testes; zinc oxide nanoparticle.