Heat shock proteins in male infertility: recent advances and clinical implications

The decline in male sperm quality has become a global concern for male reproductive health. Research indicates that heat stress is an important external factor that contributes to male infertility, potentially promoting germ cell apoptosis, disrupting redox balance, and affecting proteostasis. Recently, a growing body of research has demonstrated an association between heat stress-related proteins and male infertility. Heat shock proteins (HSPs) and their upstream transcription factors, known as heat shock factors (HSFs), constitute the core molecular system through which cells respond to heat stress. The main heat-shock protein families, including HSPA1, HSPA2, HSP90, HSP60, and small HSPs Small Heat Shock Proteins, play pivotal regulatory roles in spermatogenesis. These protein families influences the balance between germ cell repair and cell death by regulating proteostasis, oxidative homeostasis, and cell survival. The dysregulation of this system may represent an important molecular basis for heat stress-induced male infertility. This review focuses on the pathophysiological process of heat stress-induced male infertility, summarizes the potential mechanisms by which heat stress and heat stress-related proteins contribute to male infertility, and proposes a dynamic model of HSP systemic responses under heat stress. The current progress in the diagnosis and treatment of heat stress-related male infertility is summarized to provide a theoretical basis for further elucidating its pathogenesis, improving diagnostic accuracy, and guiding the developing of targeted therapeutic strategies.