Creation of a Dual-Induction Animal Model of Male Infertility and Assessment of a Targeted Antioxidant Therapy: A Multilayered Histopathological Investigation

Introduction: Oxidative stress is a well-established mediator of male infertility, but a robust animal model combining hormonal and toxicant-induced infertility remains poorly characterized. This study aimed to develop a dual-induction male infertility model in rats and evaluate the effects of targeted antioxidant therapy using N-acetylcysteine (NAC).Methods: Forty adults male Wistar rats were randomized into four groups (n=۱۰): Control (saline), Dual-Induction (estradiol + cadmium chloride), Dual + NAC Low Dose (۱۰۰ mg/kg/day), and Dual + NAC High Dose (۳۰۰ mg/kg/day). Estradiol (۰.۵ mg/kg s.c.) and cadmium chloride (۱ mg/kg i.p.) were administered for ۸ weeks. NAC was given orally for ۸ weeks starting simultaneously. Outcomes included sperm parameters, serum testosterone, oxidative stress markers, and histopathological scoring of testes and epididymides. Results: Dual-Induction rats exhibited significant reductions in sperm count (-۵۹%), motility (-۴۷%), and testosterone (-۴۸%) compared to controls (P-value<۰.۰۰۱). NAC treatment improved all parameters dose-dependently; high-dose NAC restored sperm count to ۸۷% of control values (P-value<۰.۰۱). Histological damage scores decreased significantly with NAC treatment (P-value<۰.۰۵). Oxidative stress markers showed normalized malondialdehyde and increased superoxide dismutase and glutathione peroxidase levels with NAC.Conclusions: We present a reproducible dual-induction male infertility model and demonstrate significant amelioration with NAC antioxidant therapy. This model can be used for preclinical assessment of future therapeutics.

کلیدواژه ها:

Male infertility ، animal model ، oxidative stress ، N-acetylcysteine ، histopathology ، sperm parameters