Protective Effect of Soybean Isoflavone (SI) on Testicular Damages Induced by Zinc Oxide Nanoparticles (ZnONPs) in Male Mice.

In recent years, with the increasing use of ZnONPs as a feed additive in animal diets, their potential impact on the animal reproductive system has garnered growing attention. The present study aimed to investigate the ameliorative effects of SI on ZnONPs-induced toxicities in mice. The experiment was divided into five groups (n = 8): normal saline (control), ZnONPs (50 mg/kg), ZnONPs (100 mg/kg), ZnONPs (50 mg/kg) + SI (50 mg/kg) + , ZnONPs (100 mg/kg) + SI (50 mg/kg). The experiment lasted for 45 days. Mice treated with ZnONPs exhibited a significant reduction in body weight (p < 0.05 or p < 0.01) and testicular index (p < 0.01). Severe histopathological damage was observed in the affected testes, accompanied by a marked increase in Zinc (Zn) content in both blood and testicular tissues (p < 0.01), elevated levels of apoptosis (p < 0.01), and decreased activities of antioxidant enzymes, including superoxide dismutase (SOD) (p < 0.01). RNA-seq analysis revealed that exposure to different concentrations of ZnONPs resulted in the enrichment of differentially expressed genes (DEGs) in mouse testicular tissues, primarily in pathways related to signal transduction, cell differentiation, and apoptosis. Additionally, ZnONPs were found to effectively modulate the expression levels of oxidative stress- and apoptosis-related genes via the JAK-STAT signaling pathways and MAPK signaling pathway. Furthermore, exposure to ZnONPs caused varying degrees of changes in the expressions of Stat1 (p < 0.01), Junb (p < 0.01), Ddx4 (p < 0.01)and Ar (p < 0.05 or p < 0.01) in the testicles of mice. In contrast, after SI treatment, the above abnormal changes induced by ZnONPs were significantly decreased. Finally, it could be concluded that SI could decrease the reproductive toxicities caused by ZnONPs in mice.