INVITED ORIGINAL ARTICLE
Year : 2016  |  Volume : 18  |  Issue : 2  |  Page : 282-291

Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility


1 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA
2 Department of Zoology, School of Life Sciences, Ravenshaw University, Cuttack - 751 003, Odisha, India
3 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA; Faculty of Medicine, MARA University of Technology (UiTM), Selangor, Darul Ehsan, Malaysia
4 Department of Urology, Cleveland Clinic, Cleveland, OH, USA

Correspondence Address:
Prof. Ashok Agarwal
American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1008-682X.170445

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To study the major differences in the distribution of spermatozoa proteins in infertile men with varicocele by comparative proteomics and validation of their level of expression. The study-specific estimates for each varicocele outcome were combined to identify the proteins involved in varicocele-associated infertility in men irrespective of stage and laterality of their clinical varicocele. Expression levels of 5 key proteins (PKAR1A, AK7, CCT6B, HSPA2, and ODF2) involved in stress response and sperm function including molecular chaperones were validated by Western blotting. Ninety-nine proteins were differentially expressed in the varicocele group. Over 87% of the DEP involved in major energy metabolism and key sperm functions were underexpressed in the varicocele group. Key protein functions affected in the varicocele group were spermatogenesis, sperm motility, and mitochondrial dysfunction, which were further validated by Western blotting, corroborating the proteomics analysis. Varicocele is essentially a state of energy deprivation, hypoxia, and hyperthermia due to impaired blood supply, which is corroborated by down-regulation of lipid metabolism, mitochondrial electron transport chain, and Krebs cycle enzymes. To corroborate the proteomic analysis, expression of the 5 identified proteins of interest was validated by Western blotting. This study contributes toward establishing a biomarker "fingerprint" to assess sperm quality on the basis of molecular parameters.


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