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

Background: Human life without sperm is not possible. Therefore, it is alarming that the fertilizing ability of human spermatozoa is continuously decreasing. The reasons for that are widely unknown, but there is hope that metabolomics-based investigations may be able to contribute to overcoming this problem. This review summarizes the attempts made so far. Methods: We will discuss liquid chromatography-mass spectrometry (LC-MS), gas chromatography (GC), infrared (IR) and Raman as well as nuclear magnetic resonance (NMR) spectroscopy. Almost all available studies apply one of these methods. Results: Depending on the methodology used, different compounds can be detected, which is (in combination with sophisticated methods of bioinformatics) helpful to estimate the state of the sperm. Often, but not in all cases, there is a correlation with clinical parameters such as the sperm mobility. Conclusions: LC-MS detects the highest number of metabolites and can be considered as the method of choice. Unfortunately, the reproducibility of some studies is poor, and, thus, further improvements of the study designs are needed to overcome this problem. Additionally, a stronger focus on the biochemical consequences of the altered metabolite concentrations is also required.

Automated summary

This review summarizes the attempts made so far to overcome the decreasing fertilizing ability of human spermatozoa using metabolomics-based investigations. Various analytical methods, including liquid chromatography-mass spectrometry (LC-MS), gas chromatography (GC), infrared (IR), Raman, and nuclear magnetic resonance (NMR) spectroscopy, have been discussed. Results show that LC-MS detects the highest number of metabolites and can be considered as the method of choice. However, the reproducibility of some studies is poor, and further improvements of study designs are needed, along with a stronger focus on the biochemical consequences of altered metabolite concentrations.