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

Abstract

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.

Keywords: male infertility; metabolome; semen; seminal plasma; spermatozoa.

Figure 1

Sources for variations/for differing results in untargeted metabolomics experiments divided into biological and technical influences. Biological confounders can/should be controlled by a thorough study design. Each step of a common untargeted metabolome workflow (pre-analytics, analytics, data processing and interpretation) should be as stringent as possible and thoroughly documented. This figure and the legend were taken from the open access article [65] distributed under the terms of the Creative Commons CC BY license.