Metabolomics analysis of seminal plasma in patients with idiopathic Oligoasthenoteratozoospermia using high‐resolution NMR spectroscopy

Abstract

Background Male infertility is a global health issue caused by a combination of different factors. Specialists generally rely on semen analysis to diagnose male infertility. However, it is known that diagnostic semen analysis fails to identify about 50% of male infertility disorders. Recently, metabolomics has been proven to be a powerful technique for the diagnosis of different diseases. Objective To determine whether metabolites could be used as potential biomarkers for the diagnosis of male factor infertility through comparing seminal plasma samples from infertile men with oligoasthenoteratozospermia (OAT) and samples from normozoospermic controls. Materials and methods This study utilized high‐resolution 1H NMR spectroscopy to reveal whether the metabolomic changes of seminal plasma obtained from 31 patients with oligoasthenoteratozospermia (OAT) are different from the ones obtained from 28 normozoospermic controls. Results Multivariate statistical analysis of NMR data concluded that the metabolomic profile of samples from patients with OAT exhibits statistically significant differences when compared to the controls. The differences were based on the metabolites lactate, citrate, lysine, arginine, valine, glutamine, creatinine, α‐ketoglutaric acid, spermine, putrescine, and tyrosine. Except the tyrosine, levels of the above metabolites were significantly decreased in patients with OAT compared to the controls. The levels of citrate, choline, spermine, putrescine, α‐ketoglutaric acid, valine, and tyrosine were significantly different (p < 5 × 10−4) between two groups. On the other hand, levels of lactate, creatinine, lysine, arginine, and glutamine were also statistically significant (0.001 < p < 0.05). However, considering the p‐values, the physiological relevance of these metabolites may be lower when compared to the others. A PLS‐DA model built on the NMR data achieved 89.29% sensitivity and 93.55% specificity results in a leave‐one‐out cross‐validation process. Discussion and conclusion 1H NMR spectroscopy‐based metabolomic analysis could be used as a diagnostic tool for the diagnosis of oligoasthenoteratozospermia.

1H Nuclear Magnetic Resonance of Pig Seminal Plasma Reveals Intra-Ejaculate Variation in Metabolites

“…Our data shows that the pig SP is comprised by 19 metabolites, which include amino acids, salts, nucleosides, and other organic compounds. The 1 H NMR spectra obtained for pig SP is similar to that of human SP, with all identified metabolites in pig SP also present in human SP [33,38,39]. In some of these human studies, a higher number of spectral peaks (between 31-33 peaks) and metabolites were identified compared with the results reported here, which could be due to differences in the preparation of SP samples, or in the 1 H NMR spectrometer used [33,38].…”

“…The 1 H NMR spectra obtained for pig SP is similar to that of human SP, with all identified metabolites in pig SP also present in human SP [33,38,39]. In some of these human studies, a higher number of spectral peaks (between 31-33 peaks) and metabolites were identified compared with the results reported here, which could be due to differences in the preparation of SP samples, or in the 1 H NMR spectrometer used [33,38]. The similarity between pig and human SP metabolite composition was surprising considering their different proteomic profiles [7,20].…”

“…Some studies have proposed the GPC/choline ratio as a way of discriminating between different forms of spermatogenic failure, infertility and male reproductive tract [60,80]. Moreover, other studies on humans propose GPC as a biomarker for infertility [79], since abnormal GPC levels have been related to male infertility [37,38,79,81]. These studies suggest that Cho and GPC could be potential fertility biomarkers for AI-boars.…”

“…In this regard, the study of SP components is gaining interest. In both men [32,33,[36][37][38][39] and bulls [40][41][42], SP metabolites have been linked to sperm function, pointing at a possible role as markers of sperm quality and/or fertility. These studies evidence that an in-depth metabolomic profile of SP could provide a valuable list of potential sperm quality and fertility biomarkers for AI-boars.…”

Seminal Fluid Metabolomic Markers of Oligozoospermic Infertility in Humans

“…In our study, the altered levels of choline in the seminal plasma of patients with oligozoospermia compared to control class suggested an altered choline metabolism associated with this pathological condition. Muncu et al [46] analyzed a cohort of patients with oligoasthenoteratozoospermia (OAT) by high-resolution 1 H NMR spectroscopy to reveal the metabolomic changes of seminal plasma compared to a control class. The levels of citrate, choline, spermine, putrescine, α-ketoglutaric acid, valine, and tyrosine were significantly different between the two groups.…”