Thermal modulation of CatSper activity regulates hyperactivated motility in human sperm

Sperm motility is essential for successful fertilization, with hyperactivated motility (HA) playing a critical role in sperm migration and penetration of the oocyte's protective layers. HA is regulated by intracellular Ca2+ influx through the sperm-specific CatSper channel. While CatSper activation is known to be influenced by various chemical factors, its sensitivity to physical stimuli such as temperature remain unclear. In this study, we investigated the impact of temperature on CatSper activity and HA in human sperm. The percentage of sperm exhibiting HA increased significantly in a temperature-dependent manner without affecting total motility or viability. Temperature-induced HA was dependent on CatSper-mediated Ca2+ influx, as pharmacological inhibition of CatSper abolished the response. Spectrofluorometric assays and patch-clamp experiments revealed that higher temperatures modestly but consistently enhanced CatSper activation as well as other capacitation-associated cAMP/PKA signaling pathways. These findings demonstrate that rather than acting as a dedicated thermosensor, CatSper displays physiologically relevant temperature-dependent modulation, suggesting a role for thermal cues in sperm capacitation and motility within the female reproductive tract.