Novel insights into the lipid signalling in human spermatozoa

Steven Serafini; Cristian O'Flaherty

doi:10.1093/humrep/deaf085

Novel insights into the lipid signalling in human spermatozoa

Hum Reprod. 2025 May 23:deaf085. doi: 10.1093/humrep/deaf085. Online ahead of print.

Authors

Steven Serafini^{1

2

3}, Cristian O'Flaherty^{1

2

3

4

5}

Affiliations

¹ Experimental Medicine Division, Department of Medicine, McGill University, Montréal, QC, Canada.
² Urology Division, Department of Surgery, McGill University, Montréal, QC, Canada.
³ The Research Institute, McGill University Health Centre, Montréal, QC, Canada.
⁴ Department of Anatomy and Cell Biology, McGill University, Montréal, QC, Canada.
⁵ Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.

PMID: 40409756
DOI: 10.1093/humrep/deaf085

Abstract

Infertility, affecting one in six couples worldwide, poses significant health and social challenges. While both male and female factors contribute to infertility, male infertility causes remain underexplored, with about 34% of cases classified as unexplained. A few studies focus on the role of lipids in male fertility, and some lipids are rising as key players in spermatozoa. This review highlights the importance of lipids, particularly phospholipids, neutral lipids, and glycolipids, in spermatozoa during capacitation and the acrosome reaction (AR). The dynamic lipid profile of human spermatozoa is crucial for their development, maturation, and fertilization capability. During epididymal maturation, sperm undergo crucial biochemical changes, including increased production of phosphatidylcholine and sphingomyelin, which enhance membrane integrity and mobility. Increased levels of ceramide affect membrane fluidity and signalling necessary for sperm function. As spermatozoa enter the female reproductive tract, they adjust their lipid content for capacitation and fertilization. Lipid signalling is crucial for human spermatozoa, influencing their viability and fertilization potential during transit through the female reproductive tract. Lysophosphatidic acid, abundant in seminal plasma, enhances sperm motility, facilitates the AR by promoting glycolysis and calcium influx, and is important for maintaining sperm viability. The remodelling of lipid rafts, enriched in cholesterol and sphingolipids, is essential for signal transduction and capacitation. Sphingolipids, particularly sphingosine 1-phosphate and ceramide, play significant roles in sperm capacitation and AR by promoting reactive oxygen species production and calcium signalling, respectively. Understanding these lipid dynamics will increase our knowledge of the complexity of sperm metabolism.

Keywords: acrosome reaction; lipid signalling; lipidomics; male factor infertility; redox signalling; sperm capacitation.

Abstract

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