Hou Yuyang, Wang Yupeng, Pan Mengyue, An Di, Zhong Mengling, Zhang Qi
College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.
School of Pharmaceutical Sciences, Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, People's Republic of China.
J Pharm Biomed Anal. 2025 Sep 15;263:116908. doi: 10.1016/j.jpba.2025.116908. Epub 2025 Apr 17.
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.