Uncovering sperm metabolome to discover biomarkers for bull fertility

Abstract

Background Subfertility decreases the efficiency of the cattle industry because artificial insemination employs spermatozoa from a single bull to inseminate thousands of cows. Variation in bull fertility has been demonstrated even among those animals exhibiting normal sperm numbers, motility, and morphology. Despite advances in research, molecular and cellular mechanisms underlying the causes of low fertility in some bulls have not been fully elucidated. In this study, we investigated the metabolic profile of bull spermatozoa using non-targeted metabolomics. Statistical analysis and bioinformatic tools were employed to evaluate the metabolic profiles high and low fertility groups. Metabolic pathways associated with the sperm metabolome were also reported. Results A total of 22 distinct metabolites were detected in spermatozoa from bulls with high fertility (HF) or low fertility (LF) phenotype. The major metabolite classes of bovine sperm were organic acids/derivatives and fatty acids/conjugates. We demonstrated that the abundance ratios of five sperm metabolites were statistically different between HF and LF groups including gamma-aminobutyric acid (GABA), carbamate, benzoic acid, lactic acid, and palmitic acid. Metabolites with different abundances in HF and LF bulls had also VIP scores of greater than 1.5 and AUC- ROC curves of more than 80%. In addition, four metabolic pathways associated with differential metabolites namely alanine, aspartate and glutamate metabolism, β-alanine metabolism, glycolysis or gluconeogenesis, and pyruvate metabolism were also explored. Conclusions This is the first study aimed at ascertaining the metabolome of spermatozoa from bulls with different fertility phenotype using gas chromatography-mass spectrometry. We identified five metabolites in the two groups of sires and such molecules can be used, in the future, as key indicators of bull fertility.

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

“…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.…”

“…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 ]. In addition, the relationship between SP metabolites and fertility has been evidenced in both humans [ 32 , 33 , 36 , 37 , 38 , 39 ] and cattle [ 40 , 41 ], with several metabolites that can explain male infertility in humans [ 32 , 33 , 36 , 37 , 38 , 39 ] or can potentially serve as biomarkers of bull fertility [ 40 , 41 , 42 ]. To the best of our knowledge, however, there is no information regarding the metabolomic profile of pig SP.…”

Lipidomic markers of sperm cryotolerance in cattle

“…Saturated fatty acids, especially the long-chained SFA such as 22:0, modify the fluidity of cellular membrane by increasing the energy (higher melting point) required for maintaining fluidity. In addition, it has been reported that MUFA was inversely related to post-thaw sperm viability in human sperm and these reports suggested that oleic acid may be a substrate of lipid oxidation 19,40 , which might cause a decrease in sperm motility 24,26 . However, in the current study, 18:1 cis9 (oleic acid) was more abundant in the PL fraction of Good freezability sperm.…”

Changes in Bull Semen Metabolome in Relation to Cryopreservation and Fertility

“…Lysophosphatidylcholine, formed by the hydrolysis of phosphatidylcholine, a normal component of sperm plasma membrane, influences motility, capacitation and acrosome reaction [27,28], contributing to membrane-fusion events during fertilization [68]. In a previous study, other metabolites, such as gamma-aminobutyric acid, carbamate, benzoic acid, lactic acid and palmitic acid, were identified as potential bull fertility markers, but a different method of analysis (i.e., GS-MS) was employed [20].…”

“…This approach allows for the comprehensive identification of metabolites, such as amino acids, peptides, fatty acids and carbohydrates in secretions, cells, tissues and organs [17][18][19]. Metabolomics has been recently used to identify male fertility biomarkers in farm animals, including cattle [20,21]. Seminal plasma has long been used as a key source to investigate male infertility.…”