Protective effect of soybean isoflavone (SI) on ovarian damages by zinc oxide nanoparticles (ZnONPs) in female mice.

With the wide use of ZnONPs in industry and biomedicine, their reproductive toxicity has raised great concern. Soybean isoflavone (SI), a natural antioxidant phytoestrogen, was used to alleviate ZnONPs-induced ovarian damage in mice. Five groups of mice were used: control, 50 mg/kg ZnONPs, 100 mg/kg ZnONPs, 50 mg/kg ZnONPs + 50 mg/kg SI, and 100 mg/kg ZnONPs + 50 mg/kg SI. All mice were administered daily by gavage for 45 days. Ovaries were then collected for analysis of zinc content, histopathology, apoptosis, and related protein expression. ZnONPs exposure caused severe ovarian histopathological damage and significantly elevated zinc levels in blood and ovarian tissue (P < 0.01). Body weight, ovarian index, and follicle number decreased dose-dependently, while apoptosis increased. RNA-seq revealed that ZnONPs induced oxidative stress, apoptosis, hormonal disturbance, and impaired follicular development. SI effectively reversed these alterations by enhancing antioxidant capacity, inhibiting oxidative stress-related apoptosis, and normalizing the expression of Ddx4, Er, H2ab1, and Ar, thus preserving ovarian structure and function. SI alleviates ZnONPs-induced reproductive toxicity by reducing oxidative stress, inhibiting apoptosis, and regulating hormone pathways. SI protects ovaries via the Ddx4/Er/Ar/H2ab1 network and provides a new natural intervention for nanoparticle damage.