Resveratrol mitigates heat stress-induced testicular injury in rats: enhancing male fertility via antioxidant, antiapoptotic, pro-proliferative, and anti-inflammatory mechanisms.

Abstract

This study investigates the protective effects of resveratrol (RSV) against heat stress (HS)-induced testicular injury in rats. Climate change has exacerbated heat stress, particularly affecting male fertility by impairing testicular function and sexual behavior. A total of 32 rats were allocated into four experimental groups: control, RSV control, HS control, and RSV + HS. The HS groups were subjected to a 43 °C water bath for 20 min to induce testicular hyperthermia, while the RSV + HS group received 20 mg/kg of RSV starting just before HS and continuing for eight weeks. Our findings reveal that HS significantly impairs male sexual behavior, evidenced by reduced mount and intromission numbers, and increased latencies. It also negatively affects the reproductive system, decreasing the weights of testes (Cohen's d = 1.8), epididymis, and accessory sex glands, and deteriorating sperm profile parameters such as motility (Cohen's d = 2.1), viability, and morphology. Furthermore, HS notably decreases reproductive performance in female rats, reducing litter size, live births, and conception rates. Biochemically, HS decreases activities of key antioxidant enzymes in the testes-glutathione peroxidase, superoxide dismutase, and catalase-while increasing lipid peroxidation, nitrite levels, and proinflammatory cytokines (IL-1β and TNF-α). It also reduces serum levels of reproductive hormones like testosterone (Cohen's d = 2.0) and 17β-estradiol. These results were affirmed with the histopathological evaluation and the immunohistochemistry staining (Ki-67, PCNA, Bax 5, and caspase-3 protein expression). Remarkably, RSV treatment mitigated these adverse effects, restoring both physiological and biochemical parameters toward normal levels (e.g., testicular weight Cohen's d = 1.6, sperm motility Cohen's d = 1.9, and testosterone levels Cohen's d = 1.7). This suggests that RSV's antioxidative, anti-inflammatory, antiapoptotic, and androgenic properties could effectively counteract the degenerative impacts of testicular hyperthermia. This highlights the potential of RSV as a therapeutic agent against climate change-induced fertility issues in males.