Protective effects of atorvastatin on testicular dysfunction and reduced sperm quality induced by high-fat diet in mice: The inhibitory mechanism of oxidative stress.

Obesity significantly impairs various organs through the exacerbation of oxidative stress. Atorvastatin, a lipid-lowering agent, has shown potential in treating obesity-related metabolic disorders. This study aimed to assess the impact of obesity on male testicular development and sperm quality, and to evaluate the protective role of atorvastatin. Male C57BL/6 mice were fed a high-fat diet (HFD) containing 60% fat for 8 weeks to induce obesity. Atorvastatin was administered at doses of 3, 6, or 12 mg/kg/d. The results showed that compared to the control group, HFD-fed mice exhibited significantly increased body weight, serum cholesterol, and triglyceride levels. Additionally, they showed abnormal testicular morphology, increased sperm deformity rates, and reduced sperm count and motility. HFD reduced serum testosterone levels and the expression of key steroid synthase StAR in testes, along with decreased expression of tight junction proteins Occludin and ZO-1 at the blood-testis barrier. HFD also upregulated BAX expression and downregulated BCL2 expression, with concomitant reductions in antioxidant enzyme activities (SOD, GSH-px) and increased oxidative stress, as reflected by elevated serum MDA levels. Atorvastatin treatment restored testicular and sperm health in a dose-dependent manner, enhancing testosterone synthesis, improving blood-testis barrier integrity, and mitigating apoptosis and oxidative stress. In conclusion, HFD negatively affects male reproductive health, while atorvastatin, particularly at higher doses, offers significant protection through the inhibition of oxidative stress, underscoring its potential clinical utility.