Metabolomics analysis of human spermatozoa reveals impaired metabolic pathways in asthenozoospermia

Abstract Background Infertility is a major health issue, affecting 15% of reproductive‐age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility. Methods We compared the metabolome and lipidome of spermatozoa of men with normozoospermia ( n = 44) and AS ( n = 22) using untargeted LC–MS and the metabolome of seminal fluid using 1 H‐NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate. Results We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS. Conclusions Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS.