Spermidine ameliorates heat stress-induced testicular dysfunction in mice.

While the adverse effects of heat stress on male fertility are well-established, the development of targeted intervention strategies remains a critical research gap. Spermidine, a naturally occurring polyamine in plants and animals, exhibits diverse biological functions including potential antioxidant and autophagy-modulating properties. However, its protective role in spermatogenesis under heat stress conditions requires further investigation. This study aimed to determine whether spermidine mitigates heat stress-induced spermatogenic dysfunction through antioxidant effects or autophagy regulation. Our findings revealed that 14 days post-heat exposure (Day 0 to anaesthetization), testis-to-body significantly decreased, accompanied by increased seminiferous tubule damage and reduced germ cell layers. Heat stress altered the expression of key genes involved in the testicular antioxidant-related genes (SOD1, SOD2, Nrf2), autophagy-related genes (ATG4, PINK1), mitochondrial biogenesis-related genes (DNM1L, Sirt1, Pgc-1α, Tfam), apoptosis-related genes (Bax, Bcl2, Caspase 3, Caspase 9). Additionally, while testosterone levels increased, sperm motility, sperm concentration, and cleavage rates declined, with a concomitant rise in sperm abnormalities. Notably, intraperitoneal administration of 5 mg/kg spermidine effectively counteracted these detrimental effects. These results highlight spermidine's potential as a therapeutic agent for testicular damage due to heat stress.