Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters

Xu, Yuhao; Lü, Hongmei; Wang, Yan; Zhang, Zhimin; Wu, Qian

doi:10.1016/j.jpba.2019.112888

Cited by 50 publications

(49 citation statements)

References 27 publications

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“…Several studies have already confirmed the relation between carnitines and sperm quality, linking the carnitine concentration in the seminal plasma to several sperm parameters 24‐29 and fertility 27,28,30 . More recently, metabolomic studies have confirmed a positive correlation between carnitine concentration in the seminal plasma and sperm concentration in the ejaculate 15,31 . By combining with carnitine, fatty acids form acylcarnitines, which allow their transport across the inner mitochondrial membrane to supply energy through beta‐oxidation.…”

Section: Discussionmentioning

confidence: 90%

“…Spermine also has a role in sperm decapacitation, which allows the spermatozoa to perform its acrosomal reaction at the right time 46 . Spermine concentration in the seminal plasma has been positively correlated with sperm mobility, and negatively correlated with anomalies of the intermediate piece 15,31 . Furthermore, the spermine/spermidine ratio, which measures the activity of the spermine synthase, was significantly lower in the SOA group, indicating an impairment of the polyamine biosynthetic pathway.…”

Section: Discussionmentioning

confidence: 99%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

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Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia

et al. 2020

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Background Male factor is incriminated in approximately 50% of cases of infertility. The metabolomic approach has recently been used in the assessment of sperm quality and male fertility. Materials and methods We analyzed the metabolomic signatures of the seminal plasma in 20 men with severe oligoasthenospermia (prewash total motile sperm count < 5.106) (SOA) and compared it to 20 men with normal semen parameters, with a standardized approach of targeted and quantitative metabolomics using high‐performance liquid chromatography, coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. Results Among the 188 metabolites analyzed, 110 were accurately measured in the seminal plasma. A robust model discriminating the two populations (Q2(cum) = 55.2%) was obtained by OPLS‐DA (orthogonal partial least‐squares discriminant analysis), based on the drop in concentrations of 37 metabolites with a VIP (variable important for projection) greater than 1. Overall, in men with SOA, there was a significant decrease in: 17 phosphatidylcholines and four sphingomyelins; acylcarnitines, with free L‐carnitine being the most discriminating metabolite; polyunsaturated fatty acids; six amino acids (glutamate, aspartate, methionine, tryptophan, proline, and alanine); and four biogenic amines (spermine, spermidine, serotonin, and alpha‐aminoadipate). Discussion Our signature includes several metabolic changes with different impacts on the sperm quality: a change in phospholipid composition and the saturation of their fatty acids that is potentially linked to the deterioration of sperm membranes; a carnitine deficiency that can negatively impact the energy production via fatty acid oxidation and oxidative phosphorylation; and a decreased level of amino acids and biogenic amines that can lead to dysregulated metabolic and signaling pathways. Conclusion We provide a global overview of the metabolic defects contributing to the structural and functional alteration of spermatozoa in severe oligoasthenospermia. These findings offer new insights into the pathophysiology of male factor infertility that could help to develop future specific treatments.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia

et al. 2020

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…These molecules have been demonstrated to play a key role in several biological processes, including gamete quality and function [ 31 ]. In this regard, in-depth metabolomic analyses of human SP have revealed that several metabolites are related to sperm quality parameters, such as concentration, morphology and motility [ 32 , 33 , 34 ]. The relationship between SP metabolites and sperm functionality have also been reported in humans, showing that the contribution of metabolites such as uric acid, tryptophan or taurine, maintains reactive oxidative species (ROS) at low levels in this specie [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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In pigs, ejaculate is expelled in fractions, mainly the sperm-rich fraction (SRF) and the post-SRF (PSRF), which differ in both sperm content and origin. In addition, intra-ejaculate variability between fractions in terms of sperm reproductive characteristics has been previously reported, the highest sperm quality being observed in the first 10 mL of the SRF (SRF-P1). As seminal plasma (SP) composition has been purported to influence sperm physiology, the aim of this study was to profile pig SP metabolite composition and to find putative differences between the ejaculate portions (SRF-P1, the rest of SRF [SRF-P2], PSRF) and entire ejaculate (EE). To this end, ejaculates (n = 8, one per boar) were collected in fractions and SP was analyzed using 1H Nuclear Magnetic Resonance spectroscopy. We identified 19 metabolites present in all ejaculate portions and the EE, and reported correlations between the metabolites. Additionally, and for the first time in mammals, we found intra-ejaculate variability in the SP metabolites, observing different relative abundances in choline, glycerophosphocholine and glycine. Regarding their influence in sperm physiology, we hypothesize that these metabolites may explain the specific reproductive characteristics of each ejaculate portion. Finally, the reported SP metabolites could serve as a first steppingstone in the study of quality, functionality, and fertility biomarkers.

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Changes in seminal plasma microecological dynamics and the mechanistic impact of core metabolite hexadecanamide in asthenozoospermia patients

Han,

Wang,

et al. 2024

iMeta

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Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large‐scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi‐omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS‐I), moderate AZS (AZS‐II), and severe AZS (AZS‐III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS‐I) and an AZS group (AZS‐II and AZS‐III). Correlation and cross‐reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium‐Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite‐targeting gene analysis and single‐cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.

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Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters

Cited by 50 publications

References 27 publications

Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia

Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia

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

Changes in seminal plasma microecological dynamics and the mechanistic impact of core metabolite hexadecanamide in asthenozoospermia patients

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