Mechanisms of heat stress-induced testicular damage in rats

Heat stress adversely affects male reproductive function, yet its underlying mechanisms remain incompletely understood. This study investigated the impact of heat stress on the reproductive system in adult male SD rats. Results demonstrated that heat stress significantly up-regulated testicular HSP70 expression, reduced testicular index, sperm vitality, and sperm density. Serum levels of follicle-stimulating hormone and superoxide dismutase activity were notably decreased, indicating disrupted reproductive endocrinology and impaired antioxidant capacity, respectively. Further analysis revealed that heat stress induced oxidative stress and inflammatory responses, elevating reactive oxygen species, malondialdehyde, and iron ion levels while suppressing the Nrf2 signaling pathway in rat testes. This promoted ferroptosis and NLRP3 inflammasome activation, down-regulated tight junction-related genes, and severely compromised testicular health. Additionally, heat stress altered the expression of M6A methylation and autophagy-related genes, suggesting effects on post-transcriptional modification and cellular self-degradation. Gut microbiota composition and metabolomic profiles were also significantly disturbed, indicating a potential role of gut microbiota in heat stress-induced spermatogenic damage. In conclusion, heat stress impairs testicular function through oxidative stress, inflammatory activation, metabolic disruption, and gut microbiota dysbiosis.