Sphingolipids and Male Reproductive Health: A Narrative Review of Their Roles in Spermatogenesis, Fertility, and Dysfunction.

Abstract

Sphingolipids are bioactive lipids involved in cellular signaling and structural processes. Recent studies highlight their critical role in spermatogenesis, sperm functionality, and male infertility. Key sphingolipid metabolites, such as ceramide, ceramide-1-phosphate, and sphingosine-1-phosphate, mediate signaling pathways related to apoptosis, proliferation, stress responses, necrosis, inflammation, autophagy, aging, and differentiation. This review aims to summarize recent advancements in understanding the roles of sphingolipids in spermatogenesis, sperm motility, capacitation, the acrosome reaction, and fertilization, as well as their impact on abnormal spermatogenesis, gonadal dysfunction, and infertility. A narrative review was conducted by analyzing relevant literature published primarily between 2000 and 2024, focusing on the involvement of sphingolipids in male reproductive physiology. Sphingolipids regulate various stages of spermatogenesis, including germ cell proliferation, differentiation, and apoptosis, while also modulating critical processes such as sperm maturation, membrane remodeling, and signaling during capacitation and the acrosome reaction. Dysregulation of sphingolipid metabolism contributes to abnormal spermatogenesis, oxidative stress, testicular dysfunction, and impaired sperm functionality, which are linked to male infertility. Additionally, sphingolipids are implicated in sperm-oocyte fusion, further underscoring their essential role in male fertility. Understanding the precise mechanisms of sphingolipid action may offer potential therapeutic targets for treating male infertility. Future research should focus on elucidating these mechanisms and exploring interventions to correct sphingolipid imbalances.