Seminal Fluid Metabolomic Markers of Oligozoospermic Infertility in Humans

Abstract

Infertility affects 12–15% of couples worldwide, and male factors are the cause of nearly half of all cases. Studying seminal fluid composition could lead to additional diagnostic accuracy and a better understanding of the pathophysiology of male factor infertility. Metabolomics offers a new opportunity to evaluate biomarkers and better understand pathological mechanisms. The aim of the study was to identify new markers or therapeutic targets to improve outcomes in male factor or idiopathic infertility patients. Semen samples were obtained from 29 men with a normal spermogram test, and from 18 oligozoospermic men. Samples were processed and analyzed by Nuclear Magnetic Resonance spectroscopy and, subsequently, multivariate and univariate statistical analyses. Receiving Operator Curves (ROC) and Spearman correlations were also performed. An Orthogonal Partial Least Square Discriminant Analysis supervised multivariate model was devised to compare the groups. The levels of fructose, myo-inositol, aspartate and choline were altered. Moreover, Spearman Correlation associated fructose, aspartate and myo-inositol with the total amount of spermatozoa, total motile spermatozoa, % of immotility and % of “in situ” spermatozoic motility respectively. NMR-based metabolomics allowed the identification of a specific metabolic fingerprint of the seminal fluids of patients affected by oligozoospermia.

Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia

“…Previous metabolomic studies have also reported a significant decrease in various amino acids, including the ones we identified, in the seminal plasma of men with male factor infertility 12,43 . Among these amino acids, glutamate is the most abundant in the seminal plasma, and its concentration is correlated with the sperm concentration, 31 whereas aspartate is correlated with the number and motility of the sperm 16 . Both these amino acids have been repeatedly shown to be decreased in men with male factor infertility 7,14,16,42 .…”

“…It has recently been used in the analysis of the seminal fluid in men with male factor infertility. However, there is a large heterogeneity in the methods used, the populations included, and the results reported, and no clear conclusion has been made so far 7‐16 . Moreover, the majority of these studies used the World Health Organization (WHO) reference values for sperm characteristics 17 .…”

Semen Biochemical Components in Varicocele, Leukocytospermia, and Idiopathic Infertility

“…Mirnamniha et al [35] reported that the deficiency of trace elements such as calcium copper, manganese, magnesium, zinc, and selenium is associated with impaired spermatogenesis, altered levels of sex hormones, seminal oxidative stress, inflammation, and apoptosis. Recently, Murgia et al [12] detected altered levels of fructose, myo-inositol, aspartate, and choline in oligozoospermic men. In this paper, the data regarding the analyzed variables suggested some intriguing hypotheses.…”

“…The investigation of other different semen biochemical components may explain their role in seminal pathologies. Recently, Murgia et al [ 12 ] indicated that seminal fluid metabolome may represent a marker for oligozoospermia. Moreover, the identification of the lipids most closely related to the reproductive success may be of great interest to the scientific community.…”

Proteomics and metabolomics — Current and future perspectives in clinical andrology

“…On the other hand, amino acids, citric acid, choline, D‐glucose, myo‐inositol, lactate and pyruvate were significantly overexpressed in infertile teratozoospermic patients (Mehrparvar et al., 2020). In oligozoospermic patients, 1 H‐NMR detected altered levels of fructose, myo‐inositol, aspartate and choline, involved in the sperm maturation, energy metabolism and cell membrane composition (Murgia et al., 2020). Future in‐depth studies are required to better investigate the seminal metabolome and identify biomarkers associated with sperm abnormalities.…”