Research Article: Metabolomic profiling reveals correlations between spermiogram parameters and the metabolites present in human spermatozoa and seminal plasma

Date Published: February 20, 2019

Publisher: Public Library of Science

Author(s): Kathrin M. Engel, Sven Baumann, Ulrike Rolle-Kampczyk, Jürgen Schiller, Martin von Bergen, Sonja Grunewald, Roberto Amendola.


In 50% of all infertility cases, the male is subfertile or infertile, however, the underlying mechanisms are often unknown. Even when assisted reproductive procedures such as in vitro fertilization and intracytoplasmic sperm injection are performed, the causes of male factor infertility frequently remain elusive. Since the overall activity of cells is closely linked to their metabolic capacity, we analyzed a panel of 180 metabolites in human sperm and seminal plasma and elucidated their associations with spermiogram parameters. Therefore, metabolites from a group of 20 healthy donors were investigated using a targeted LC-MS/MS approach. The correlation analyses of the amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and sugars from sperm and seminal plasma with standard spermiogram parameters revealed that metabolites in sperm are closely related to sperm motility, whereas those in seminal plasma are closely related to sperm concentration and morphology. This study provides essential insights into the metabolome of human sperm and seminal plasma and its associations with sperm functions. This metabolomics technique could be a promising screening tool to detect the factors of male infertility in cases where the cause of infertility is unclear.

Partial Text

Fertility problems are increasingly occurring in couples worldwide, and male factors are involved in approximately 50% of all infertility cases [1]. To predict male reproductive potential and record treatment success, clinicians currently primarily rely on semen analyses conducted according to the guidelines of the World Health Organization (WHO) [2]. This protocol comprises the determination of rather superficial parameters, such as semen volume, semen pH, sperm cell count, sperm motility, and sperm morphology. With the exception of motility these parameters do not allow the detailed assessment of the functional status of the sperm cell. Therefore, the causes of male factor infertility frequently remain elusive even when assisted reproductive procedures such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are performed.

Despite the standardization of the experimental procedure, high deviations were observed for some analytes (S2 Table), possibly as a result of interindividual differences. The normalization to 100 × 106 sperm cells could also contribute to the deviations because the concentrations of “0” remain unaffected by this normalization. However, this normalization is less error-prone than dilution of the samples or the attempt to concentrate the samples to 100 × 106 sperm cells prior to MS analysis. The results of the seminal plasma analysis are more reliable than those of the sperm analysis.

Here, we present the first targeted approach to a metabolomic analysis of human sperm and seminal plasma using sophisticated and reliable sample preparation methods and liquid chromatography/flow injection analysis coupled with electrospray ionization mass spectrometry under high-throughput conditions. This pilot study is a first step in linking traditional spermiogram parameters with sophisticated mass spectrometric tools. Although further studies will be necessary to define the normal range in the concentrations of the metabolites in the sperm and seminal plasma of healthy men, the multiple correlations with standard sperm parameters found in this study demonstrate that metabolomics is a very useful tool in the identification of biomarkers for male infertility. As a next step, metabolomic investigations of semen samples from subfertile and infertile men should be performed.




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