The mammalian testis is a highly organized organ essential for male reproduction. Its structure comprises seminiferous tubules lined with Sertoli cells, which support spermatogenesis, surrounded by peritubular myoid cells. Within the connective tissue framework lie the Leydig cells, which synthesize testosterone in response to luteinizing hormone. Research has highlighted the importance of various ion channels and proteins in testicular function. The TWINK-related acid-sensitive potassium channel 1 (TASK-1), a two-pore channel, is vital for several physiological functions in the testis. Furthermore, Leydig cells uniquely express several key proteins, including c-kit, and platelet-derived growth factor receptor α. The co-expression of these proteins, including TASK-1, in Leydig cells suggest the presence of complex regulatory mechanisms critical for modulating testosterone production, release, and overall testicular function. Transient receptor potential vanilloid-1 (TRPV1), a member of the transient receptor potential channel family, also plays a crucial role in testicular function, influencing processes such as sensory function, steroidogenesis, and sperm function. Hormonal fluctuations and aging affect both the presence and function of TRPV1. This channel is thought to contribute programmed cell death within the testes, particularly impacting Leydig cell survival. Notably, testosterone appears to counteract these detrimental effects by downregulating TRPV1 expression, indicating a complex interplay between TRPV1, testosterone, and overall testicular function. Therefore, we aim to discuss the critical role of ion channels, specifically focusing on TASK-1 and TRPV1 channels, in the physiological and pathophysiological functions of testicular cells.

The role of transient receptor potential vanilloid receptor-1 (TRPV1) has been primarily investigated in pain sensory neurons. Relatively, little research has been performed in testicular cells. TRPV1 is abundantly expressed in Leydig cells of young adult mice. This study was conducted to determine the role of the TRPV1 channel in Leydig cells. TRPV1 modulators and testosterone were treated to the mouse Leydig cell line TM3 cells for 24 h. Capsaicin, a TRPV1 activator, dose-dependently induced cell death, whereas capsazepine, a TRPV1 inhibitor, inhibited capsaicin-induced cell death. Testosterone treatment reduced capsaicin-induced cell death. High concentrations of testosterone decreased TRPV1 mRNA and protein expression levels. However, TRPV1 modulators did not affect testosterone production. These results showed that capsaicin induced cell death of Leydig cells and that testosterone reduced capsaicininduced cell death. Our findings suggest that testosterone may regulate the survival of Leydig cells in young adult mice by decreasing the expression level of TRPV1.

Reproductive potential decreases with age. A decrease in male fertility is due to a combination of morphological and molecular alterations in the testes. Transient receptor potential vanilloid receptor-1 (TRPV1) is associated with aging and lifespan, and its activation causes apoptotic cell death in various cell types. However, the effect of TRPV1 on testicular apoptosis in aged mice has not yet been reported. TRPV1 knockout (KO) mice had a longer lifespan than that of wild-type (WT) mice. Lifespan was increased by 11.8% in male TRPV1 KO mice compared to that in WT mice. TRPV1 KO males lived approximately 100 days longer than WT males on average, and the maximum lifespan was markedly extended in TRPV1 KO mice compared with that in WT mice. The TRPV1 expression levels were highly increased in the testes of older mice. TRPV1 was expressed in the entire testes region of the old mice. In addition, old TRPV1 KO mice had lower testicular apoptosis than that of WT mice. Our results show that TRPV1 induces testicular apoptosis and suggest that TRPV1 may be associated with testicular aging.