Male infertility has become a global health problem. Currently, the diagnosis of
male infertility depends on the results of semen quality or requires invasive surgical intervention. The process is complex and time-consuming. Metabolomics is an emerging platform with unique advantages in disease diagnosis and pathological mechanism research. In this study, ultra-performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry (UPLC-ESI-IT-TOFMS) combined with chemometrics methods was used to discover potential
biomarkers of
male infertility based on non-targeted plasma metabolomics. Plasma samples from healthy controls (HC, n = 43) and various types of infertile patients, i.e., patients having
oligozoospermia (OS, n = 36), asthenospermia (AS, n = 56) and
erectile dysfunction (ED, n = 45) were analyzed by UPLC-ESI-IT-TOFMS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. The results of OPLS-DA showed that HCs could be discriminated from infertile patients including OS (R 2 = 0.903, Q 2 = 0.617, AUC = 0.992), AS (R 2 = 0.985, Q 2 = 0.658, AUC = 0.999) or ED (R 2 = 0.942, Q 2 = 0.500, AUC = 0.998). Some potential
biomarkers were successfully discovered by variable selection methods and variable important in the projection (VIP) in combination with the T-test. Statistical significance was set at p < 0.05; the Benjamini-Hochberg false discovery rate was used to reduce type 1 errors resulting from multiple comparisons. The identified
biomarkers were associated with energy consumption,
hormone regulation and
antioxidant defenses in spermatogenesis. To elucidate the pathophysiology of
male infertility, relative metabolic pathways were studied. It was found that
male infertility is closely related to disturbed
phospholipid metabolism,
amino acid metabolism,
steroid hormone biosynthesis metabolism, metabolism of
fatty acids and products of
carnitine acylation, and
purine and
pyrimidine metabolisms. Plasma metabolomics provides a novel strategy for the diagnosis of
male infertility and offers a new insight to study pathogenesis mechanism.