A review of cellular and molecular interactions between endocannabinoids and male fertility: Balancing beneficial and detrimental effects.

The endocannabinoid system (ECS) has significant potential to influence male reproductive functions by targeting both the central nervous system and peripheral tissues, thereby promoting testicular homeostasis. Endogenous cannabinoids (eCBs) play an important role in regulating reproductive hormones, spermatogenesis, sperm motility, maturation, and function, all crucial for successful fertilization. However, excessive amounts of eCBs disrupt the function of testicular cells, leading to impaired sperm production, reduced motility and capacitation, premature acrosome response, and enhanced apoptosis. Despite these findings, the cellular and molecular mechanisms underlying the implications of eCBs in male reproduction remain unclear. This review is an attempt to provide an insight into the main mechanisms activated by the cross-talk between the ECS and male (in)fertility. The information presented in this report was obtained through an extensive review of scientific literature from various databases, including Web of Science, PubMed, Elsevier, Scopus, and Google Scholar. The reviewed studies suggest that oxidative stress, inflammation, and apoptosis are among the major modulatory mechanisms through which the ECS may contribute to male (in)fertility. This knowledge may lead to the development of potential clinical applications targeting endocannabinoid signaling to address infertility and enhance reproductive health in men.