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Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species.

ABSTRACT: BACKGROUND:Reactive oxygen species (ROS) plays a major role in the pathology of male infertility. It is an independent biomarker of sperm function. Seminal plasma is a natural reservoir of antioxidants responsible for the nourishment, protection, capacitation, and motility of sperm within the female reproductive tract resulting in successful fertilization and implantation of the embryo. A comparative proteomic analysis of seminal plasma proteins from fertile men and infertile men with varying levels of ROS was carried out to identify signature proteins involved in ROS-mediated reproductive dysfunction. METHODS:A total of 42 infertile men presenting with infertility and 17 proven fertile donors were enrolled in the study. ROS levels were measured in the seminal ejaculates by chemiluminescence assay. Infertile men were subdivided into Low ROS (0-<93 RLU/s/10(6) sperm; n = 11), Medium ROS (>93-500 RLU/s/10(6) sperm; n = 17) and High ROS (>500 RLU/s/10(6) sperm; n = 14) groups and compared with fertile men (4-50 RLU/s/10(6) sperm). 4 subjects from fertile group and 4 each from the Low, Medium and High ROS were pooled. 1D gel electrophoresis followed by in-gel digestion and LC/MS-MS in a LTQ-Orbitrap Elite hybrid mass spectrometer system was used for proteome analysis. Identification of differentially expressed proteins (DEPs), their cellular localization and involvement in different pathways were examined utilizing bioinformatics tools. RESULTS:The results indicate that proteins involved in biomolecule metabolism, protein folding and protein degradation are differentially modulated in all three infertile patient groups in comparison to fertile controls. Membrane metallo-endopeptidase (MME) was uniformly overexpressed (>2 fold) in all infertile groups. Pathway involving 35 focus proteins in post-translational modification of proteins, protein folding (heat shock proteins, molecular chaperones) and developmental disorder was overexpressed in the High ROS group compared with fertile control group. MME was one of the key proteins in the pathway. FAM3D was uniquely expressed in fertile group. CONCLUSION:We have for the first time demonstrated the presence of 35 DEPs of a single pathway that may lead to impairment of sperm function in men with Low, Medium or High ROS levels by altering protein turn over. MME and FAM3D along with ROS levels in the seminal plasma may serve as good markers for diagnosis of male infertility.

SUBMITTER: Agarwal A

PROVIDER: S-EPMC4552280 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species.

Agarwal Ashok A Ayaz Ahmet A Samanta Luna L Sharma Rakesh R Assidi Mourad M Abuzenadah Adel M AM Sabanegh Edmund E

Clinical proteomics 20150828 1

<h4>Background</h4>Reactive oxygen species (ROS) plays a major role in the pathology of male infertility. It is an independent biomarker of sperm function. Seminal plasma is a natural reservoir of antioxidants responsible for the nourishment, protection, capacitation, and motility of sperm within the female reproductive tract resulting in successful fertilization and implantation of the embryo. A comparative proteomic analysis of seminal plasma proteins from fertile men and infertile men with va ...[more]

PMID: 26321892

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Project description:Semen quality is the most important indicator in evaluating drake fecundity. At present, the low semen quality has become a major factor restricting the development of artificial insemination (AI) technology in ducks. Numerous studies have indicated that seminal plasma proteins play a crucial role in semen quality, but the mechanism of seminal plasma proteins regulating semen quality of drakes remains unclear. Thus, the objective of this study was to identify seminal plasma proteins associated with semen quality by comparing the seminal plasma proteomic profile of drakes with high-quality semen (HQS) and low-quality semen (LQS). Using a label-free MS-based method, a total of 745 seminal plasma proteins were identified. Of these, 55 differentially expressed proteins (DEPs) were identified (40 up-regulated and 15 down-regulated). Gene Ontology (GO) analysis showed that the DEPs were mainly enriched in transmembrane transport, extracellular matrix structural constituent, transferase activity, transferring acyl groups other than amino-acyl groups, transmembrane transporter activity, and integral component of membrane (P < 0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis indicated that the DEPs were significantly enriched in apoptosis, tyrosine metabolism, glycerophospholipid metabolism, and sulfur metabolism pathways (P < 0.05). Moreover, through protein-protein interaction (PPI) network analysis, eight potential candidate proteins were identified, including P19140 (Alpha-enolase), R0KUV7 (Calreticulin), R0K3X3 (Solute carrier family 2, facilitated glucose transporter member 5), R0L6V0 (Proteasome subunit beta), R0JKW0 (Cytochrome c), R0JMC5 (Tubulin alpha chain), R0LCK1 (Cathepsin C), and R0JUP6 (Cathepsin D), which could play crucial roles in semen quality. Notably, further analysis demonstrated that key protein P19140 (Alpha-enolase) might can control the semen quality of drakes by regulating the expression of proteins related to apoptosis pathway. This study is the first systematically comparing the seminal plasma proteome of drakes exhibiting high and low semen quality. These results provide novel insights into the mechanisms regulating semen quality of drakes.

Project description:PurposeThis study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.MethodsSemen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS < 20), group 2 (n = 38): mild (20 ≤ ROS < 40), group 3 (n = 31): moderate (40 ≤ ROS < 60), and group 4 (n = 43): high (ROS ≥ 60). A comprehensive analysis of SP and semen parameters, including conventional semen characteristics, measurement of total antioxidant capacity (TAC), sperm DNA fragmentation index (DFI), chromatin maturation index (CMI), H19-Igf2 methylation status, and untargeted seminal metabolic profiling using nuclear magnetic resonance spectroscopy (1H-NMR), was carried out.Result(s)The methylation status of H19 and Igf2 was significantly different in specimens with high ROS (P < 0.005). Metabolic fingerprinting of these SP samples showed upregulation of trimethylamine N-oxide (P < 0.001) and downregulations of tryptophan (P < 0.05) and tyrosine/tyrosol (P < 0.01). High ROS significantly reduced total sperm motility (P < 0.05), sperm concentration (P < 0.001), and seminal TAC (P < 0.001) but increased CMI and DFI (P < 0.005). ROS levels have a positive correlation with Igf2 methylation (r = 0.19, P < 0.05), DFI (r = 0.40, P < 0.001), CMI (r = 0.39, P < 0.001), and trimethylamine N-oxide (r = 0.45, P < 0.05) and a negative correlation with H19 methylation (r = - 0.20, P < 0.05), tryptophan (r = - 0.45, P < 0.05), sperm motility (r = - 0.20, P < 0.05), sperm viability (r = - 0.23, P < 0.01), and sperm concentration (r = - 0.30, P < 0.001).Conclusion(s)Results showed significant correlation between ROS levels and H19-Igf2 gene methylation as well as semen parameters. These findings are critical to identify idiopathic male infertility and its management through assisted reproduction technology (ART).

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Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species.

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Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species.

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