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

PLoS One. 2019 Jul 5;14(7):e0219179. doi: 10.1371/journal.pone.0219179. eCollection 2019.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthenozoospermia / metabolism
  • Biomarkers / metabolism
  • China
  • Gas Chromatography-Mass Spectrometry / methods
  • Humans
  • Infertility, Male / blood
  • Infertility, Male / metabolism*
  • Lipid Metabolism / physiology
  • Male
  • Metabolic Networks and Pathways / physiology
  • Metabolomics / methods
  • Oligospermia / metabolism
  • Oxidative Stress / physiology
  • Plasma / metabolism*
  • Semen / metabolism*
  • Semen Analysis / methods


  • Biomarkers

Grant support

This work was supported by National Natural Science Foundation of China. Grant numbers awarded to HM. L includes 21675174 and 21873116. Grant numbers awarded to JK. L includes 81774322. All these funds can be found at website: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.