Relative abundance of lipid metabolites in spermatozoa across three compartments

Background: Male fertility, as manifest by the quantity and progressive motility of spermatozoa, is negatively impacted by obesity, dyslipidaemia and metabolic disease. Howev-er, the relative distribution of lipids in spermatozoa and the two compartments which supply lipids for spermatogenesis (seminal fluid and blood serum) has not been studied. We hypothe-sised that altered availability of lipids in blood serum and seminal fluid may affect the lipid composition and progressive motility of sperm. Methods: 60 men of age 35 years (median (range 20 - 45) and BMI 30.4 kg/m2 (24 - 36.5) under preliminary investigation for subfertility were recruited at an NHS clinic. Men provided sam-ples of serum and semen, subject to strict acceptance criteria, for analysis of spermatozoa count and motility. Blood serum (n=60), spermatozoa (n=26) and seminal fluid (n=60) were frozen for batch lipidomics analysis. Results: Spermatozoa and seminal fluid had comparable lipid composition, but showed marked differences with the serum lipidome. Spermatozoa demonstrated high abundance of ceramides, very-long-chain fatty acids (C20-22), and certain phospholipids (sphingomyelins, plasmalogens, phosphatidylethanolamines) with low abundance of phosphatidylcholines, cholesterol and tri-glycerides. Men with spermatozoa of low progressive motility had evidence of fewer concentra-tion gradients for many lipid species between blood serum and spermatozoa compartments. Conclusion: Spermatozoa are abundant in multiple lipid species which are likely to contribute to key cellular functions. Lipid metabolism shows reduced regulation between compartments in men with spermatozoa with reduced progressive motility.
CLM is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712) and the European Foundation for the Study of Diabetes – Novo Nordisk Foundation Future Leaders’ Award (NNF19SA058974). SF and AK acknowledge funding from the BBSRC (BB/M027252/1). This research was supported by the NIHR Cambridge BRC, the core biochemical assay laboratory (CBAL) and the core metabolomic and lipidomic laboratory (CMAL). The views expressed are those of the au-thor(s) and not necessarily those of the NIHR or the Department of Health and Social Care.