Characterizing semen abnormality male infertility using non-targeted blood plasma metabolomics

Semen abnormality (SA) male infertility has become a worldwide reproductive health problem. The invasive tests (e.g., testicular biopsy) and labor-intensive methods of semen collection severely inhibit diagnosis of male infertility. In addition, the pathogenesis and biological interpretation of male infertility are still obscure. In this report, a total of 84 semen abnormality (SA) patients, diagnosed as teratozoospermia (TE, n = 21), asthenozoospermia (AS, n = 23), oligozoospermia (OL, n = 20), azoospermia (AZ, n = 20), and age-matched healthy controls (HC, n = 29) were analyzed by GC-MS for discrimination analysis and discovery of potential biomarkers. Twenty-three biomarkers were obtained by multivariate statistical method (partial least squares-discriminant analysis, PLS-DA) and univariate statistical method (analysis of variance, ANOVA) with comparisons of TE versus HC, AS versus HC, OL versus HC and AZ versus HC. Based on those biomarkers, the most relevant pathways were mainly associated with the metabolism of carbohydrates, amino acids, and lipids. The principal metabolic alternations in SA male infertility included increased levels of energy-related metabolisms, such as tricarboxylic acid cycle, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine, threonine metabolism and saturated fatty acid metabolism. Furthermore, increased levels of glutathione metabolism were related to oxidative stress. Finally, decreased levels of arginine and proline metabolism and inositol phosphate metabolism were observed. In conclusion, blood plasma metabolomics is powerful for characterizing metabolic disturbances in SA male infertility. From metabolic pathway analysis, energy production, oxidation stress and the released enzyme during spermatogenesis take the primary responsibilities for SA male infertility.