Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men.

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.

Antioxidants (Basel, Switzerland). 2019 Oct 16*** epublish ***

Ashok Agarwal, Manesh Kumar Panner Selvam, Luna Samanta, Sarah C Vij, Neel Parekh, Edmund Sabanegh, Nicholas N Tadros, Mohamed Arafa, Rakesh Sharma

American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. ., American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. ., American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. ., Department of Urology, Cleveland Clinic, Cleveland, OH 44195, USA. ., Department of Urology, Cleveland Clinic, Cleveland, OH 44195, USA. ., Department of Urology, Cleveland Clinic, Cleveland, OH 44195, USA. ., Division of Urology, Southern Illinois University School of Medicine, Springfield, IL 62769, USA. ., Department of Urology, Hamad Medical Corporation, Doha 00974, Qatar. ., American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. .

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