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

Abstract

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 and l ‐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.

Metabolomics of Human Semen: A Review of Different Analytical Methods to Unravel Biomarkers for Male Fertility Disorders

“…Only a few months later, another Chinese group published their results on a similar study using the same equipment, but a column temperature of 25 °C, also investigating the SP of AS men ( n = 20) compared to controls ( n = 20) [ 43 ]. Healthy controls were assigned based on normal CASA results.…”

Assessment of Blood Plasma Free-amino Acid Levels in Infertile Men

“…Thirdly, despite the use of serum samples in this study, it would be interesting to measure free AA levels in other body fluids. In fact, several studies have analyzed the metabolomic signature of the seminal plasma from infertile men (8,25,26). For example, a significant decrease in multiple metabolites, including alanine, aspartic acid, glutamic acid, methionine, proline, and tryptophan, was observed in men with severe oligoasthenospermia (8).…”

“…For example, a significant decrease in multiple metabolites, including alanine, aspartic acid, glutamic acid, methionine, proline, and tryptophan, was observed in men with severe oligoasthenospermia (8). Finally, in order to obtain more comprehensive results on this topic, new sophisticated approaches should be considered, such as network and metabolomic analyses (2,19,25,26).…”

Multigenerational Exposure to Uranium Changes Sperm Metabolome in Rats

“…Metabolomics have already demonstrated their ability to identify the mechanisms involved in male infertility by monitoring the metabolomes of human and rodent sperm [ 29 , 30 ]. Mass spectrometry-based methods have already proved to be extremely useful in identifying metabolites in human sperm in case of fertility problems or in asthenozoospermic patients [ 24 , 31 ]. To the best of our knowledge, there are no published reports on the application of MS-based methods to rat sperm with the exception of a few proteome-based studies [ 32 , 33 ].…”