Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm

It has long been thought that exocytosis was driven exclusively by well-studiedfusion proteins. Some decades ago, the role of lipids became evident andescalated interest in the field. Our laboratory chose a particular cell to facethis issue: the human sperm. What makes this cell special? Sperm, as terminalcells, are characterized by their scarcity of organelles and the complete absenceof transcriptional and translational activities. They are specialized for a singularmembrane fusion occurrence: the exocytosis of the acrosome. This unique traitmakes them invaluable for the study of exocytosis in isolation. We will discuss thelipids’ role in human sperm acrosome exocytosis from various perspectives, witha primary emphasis on our contributions to the field. Sperm cells have a uniquelipid composition, very rare and not observed in many cell types, comprising ahigh content of plasmalogens, long-chain, and very-long-chain polyunsaturatedfatty acids that are particular constituents of some sphingolipids. This reviewendeavors to unravel the impact of membrane lipid composition on the properfunctioning of the exocytic pathway in human sperm and how this lipid dynamicinfluences its fertilizing capability. Evidence from our and other laboratoriesallowed unveiling the role and importance of multiple lipids that driveexocytosis. This review highlights the role of cholesterol, diacylglycerol, andparticular phospholipids like phosphatidic acid, phosphatidylinositol 4,5-bisphosphate, and sphingolipids in driving sperm acrosome exocytosis.Furthermore, we provide a comprehensive overview of the factors and enzymesthat regulate lipid turnover during the exocytic course. A more thorough grasp ofthe role played by lipids transferred from sperm can provide insights into certaincauses of male infertility. It may lead to enhancements in diagnosing infertility andtechniques like assisted reproductive technology (ART).