Metabolomic characterization of semen from asthenozoospermic patients using ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry

Asthenozoospermia (AS) is a common factor of male infertility, and its pathogenesis remains unclear. The purpose of this study was to investigate the differential seminal plasma metabolic pattern in asthenozoospermic men and to identify potential biomarkers in relation to spermatogenic dysfunction using sensitive ultra-high-performance liquid chromatography-tandem quadruple time-of-flight MS (UHPLC-Q-TOF/MS). The samples of seminal plasma from patients with AS (n = 20) and healthy controls (n = 20) were checked and differentiated by UHPLC-Q-TOF/MS. Compared with the control group, the AS group showed a total of nine significantly different metabolites, including increases in creatinine, uric acid, N-6-methyladenosine (m(6)A), uridine, and taurine and decreases in carnitine, nicotinamide,N-acetylputrescine andl-palmitoylcarnitine. By analyzing the correlation among these metabolites and clinical computer-assisted semen analysis reports, we found that m(6)A is significantly correlated with not only the four decreased metabolites but also with sperm count, motility, and curvilinear velocity. Furthermore, nicotinamide was shown to correlate with other identified metabolites, indicating its important role in the metabolic pathway of AS. Current results implied that sensitive untargeted seminal plasma metabolomics could identify distinct metabolic patterns of AS and would help clinicians by offering novel cues for discovering the pathogenesis of male infertility.