Sperm metabolomic profiles of varicocele-associated asthenozoospermia

Varicocele is a leading cause of male infertility, with asthenozoospermia being a common phenotype. The metabolic basis of varicocele-induced asthenozoospermia remains poorly understood, necessitating a comprehensive metabolic profiling study. This GC-MS-based metabolomic study investigated sperm metabolic profiles across three cohorts: healthy controls (HC, n = 30), varicocele patients with normal motility (VC, n = 30), and varicocele-associated asthenozoospermia cases (VA, n = 30). Multivariate analyses (Principal Component Analysis, Partial Least Squares Discriminant Analysis, and Orthogonal Partial Least Squares Discriminant Analysis) of 85 identified endogenous metabolites revealed progressive metabolic dysregulation: 25 differential metabolites (including cysteine, leucine, glycine) distinguished VC from HC, while 29 additional perturbations (valine, threonine, alanine) characterized VA cases. These findings systematically delineate varicocele-related metabolic disturbances, providing mechanistic insights into sperm motility impairment and potential therapeutic targets for male infertility management.