Amelioration of obesity-induced testicular dysfunction and structural damage by ganoderma lucidum polysaccharides and triterpenoids in rats: Correlation with Nrf2-mediated antioxidant response.

Obesity is a global health crisis and a critical risk factor for male infertility, impairing testicular structure and function through hormonal imbalance and oxidative stress. Current therapeutic strategies are often unsatisfactory due to limited efficacy or adverse effects. This study investigated the protective effects and potential molecular mechanisms of Ganoderma lucidum (GL) polysaccharides and triterpenoids against testicular injury in high-fat diet-induced obese male rats. After 12-week GL intervention, reproductive function in obese male rats showed improvement: GL increased litter size, improved sperm motility, reduced sperm DNA fragmentation, and restored serum testosterone, inhibin B, and leptin levels. It also alleviated testicular histopathological damage, downregulated PPT1, and maintained vimentin expression. Notably, GL facilitated delayed fertility recovery and showed a trend toward improved cumulative reproductive success, although fixed-time pregnancy rates were not significantly changed. Mechanistically, GL is associated with enhanced Nrf2 pathway activity, increased SOD1, HO-1, NQO1, and GPX4 levels, and decreased MDA and ROS accumulation, thereby attenuating oxidative stress. It preserved mitochondrial integrity, suppressed germ cell apoptosis (downregulating Bax and caspase-3, upregulating Bcl-2), and promoted cell proliferation. These findings indicate that GL polysaccharides and triterpenoids effectively ameliorate obesity-induced testicular dysfunction, and these beneficial effects are associated with Nrf2-mediated antioxidant responses, mitochondrial homeostasis, apoptosis regulation, and hormonal balance. GL may serve as a promising candidate for obesity-related male infertility.