Abstract
Antioxidant supplementation in idiopathic male infertility has a beneficial effect on semen parameters. However, the molecular mechanism behind this effect has not been reported. The objective of this study was to evaluate the sperm proteome of idiopathic infertile men pre- and post-antioxidant supplementation. Idiopathic infertile men were provided with oral antioxidant supplementation once daily for a period of 6 months. Of the 379 differentially expressed proteins (DEPs) between pre- and post-antioxidant treatment patients, the majority of the proteins (n = 274) were overexpressed following antioxidant treatment. Bioinformatic analysis revealed the activation of oxidative phosphorylation pathway and upregulation of key proteins involved in spermatogenesis, sperm maturation, binding of sperm, fertilization and normal reproductive function. In addition, the transcriptional factors associated with antioxidant defense system (PPARGC1A) and free radical scavenging (NFE2L2) were predicted to be functionally activated post-treatment. Key DEPs, namely, NDUFS1, CCT3, PRKARA1 and SPA17 validated by Western blot showed significant overexpression post-treatment. Our novel proteomic findings suggest that antioxidant supplementation in idiopathic infertile men improves sperm function at the molecular level by modulating proteins involved in CREM signaling, mitochondrial function and protein oxidation. Further, activation of TRiC complex helped in nuclear compaction, maintenance of telomere length, flagella function, and expression of zona pellucida receptors for sperm–oocyte interaction.
Highlights
Despite advances in the field of male reproductive health, idiopathic male infertility remains a challenging condition to diagnose and manage
From a total of 2137 proteins present in both the groups, 379proteins proteinsin were as DEPstreatment
2137Furthermore, proteins present both groups, 379 proteins were identified as differentially expressed proteins (DEPs)
Summary
Despite advances in the field of male reproductive health, idiopathic male infertility remains a challenging condition to diagnose and manage. Increased OS has deleterious effects on semen parameters such as sperm concentration, motility and progressive motility [6,7] and it induces sperm DNA fragmentation (SDF) [2,8,9,10] resulting in male infertility. Several studies have reported the beneficial effect of antioxidants on semen parameters. Oral intake of individual antioxidants or a combination of several antioxidants such as l-carnitine, selenium, N-acetyl-cysteine, Coenzyme Q10, ubiquinol, vitamin E, vitamin C, and lycopene have led to improvement in semen parameters and sperm DNA integrity of idiopathic infertile men [11,12,13,14,15]
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