Mohammadpour-Asl Shadi, Parvin Ali, Akbari-Gharalari Naeimeh, Asadi Negar, Pooryai Araz, Roshan-Milani Shiva
Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran; Student Committee of Medical Education Development, Education Development Center, Urmia University of Medical Sciences, Urmia, Iran.
Life Sci. 2025 Sep 15;377:123778. doi: 10.1016/j.lfs.2025.123778. Epub 2025 May 29.
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.
内源性大麻素系统（ECS）通过作用于中枢神经系统和外周组织，对男性生殖功能具有显著影响，从而促进睾丸内环境稳态。内源性大麻素（eCBs）在调节生殖激素、精子发生、精子活力、成熟及功能方面发挥着重要作用，而这些对于成功受精均至关重要。然而，过量的eCBs会破坏睾丸细胞的功能，导致精子生成受损、活力和获能降低、顶体反应过早以及细胞凋亡增加。尽管有这些发现，但eCBs在男性生殖中作用的细胞和分子机制仍不清楚。本综述旨在深入探讨ECS与男性生育（不育）之间相互作用所激活的主要机制。本报告中的信息是通过广泛查阅包括科学网、PubMed、爱思唯尔、Scopus和谷歌学术在内的各种数据库中的科学文献获得的。综述研究表明，氧化应激、炎症和细胞凋亡是ECS可能影响男性生育（不育）的主要调节机制。这一知识可能会推动针对内源性大麻素信号通路的潜在临床应用的开发，以解决男性不育问题并改善生殖健康。
