Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility

No AccessJournal of UrologyAdult Urology1 Aug 2018Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility Luna Samanta, Ashok Agarwal, Nirlipta Swain, Rakesh Sharma, Banu Gopalan, Sandro C. Esteves, Damayanthi Durairajanayagam, and Edmund Sabanegh Luna SamantaLuna Samanta American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio Redox Biology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Odisha, India More articles by this author , Ashok AgarwalAshok Agarwal American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Nirlipta SwainNirlipta Swain American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio Redox Biology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Odisha, India More articles by this author , Rakesh SharmaRakesh Sharma American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Banu GopalanBanu Gopalan Yorg Corp., Plano, Texas More articles by this author , Sandro C. EstevesSandro C. Esteves ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, Brazil More articles by this author , Damayanthi DurairajanayagamDamayanthi Durairajanayagam Discipline of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia More articles by this author , and Edmund SabaneghEdmund Sabanegh Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.03.009AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility. Materials and Methods: We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured. Results: We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele. Conclusions: Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients. References 1 : Epidemiology of varicocele. Asian J Androl2016; 18: 179. 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Google Scholar © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byAtala A (2018) Re: PrESOgenesis: A Two-Layer Multi-Label Predictor for Identifying Fertility-Related Proteins Using Support Vector Machine and Pseudo Amino Acid Composition ApproachJournal of Urology, VOL. 201, NO. 1, (34-34), Online publication date: 1-Jan-2019. Volume 200Issue 2August 2018Page: 414-422Supplementary Materials Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.KeywordsproteomicstestisspermatozoamitochondriavaricoceleAcknowledgmentsResearchers who critically read the manuscript and provided useful suggestions: Drs. Ahmad Majzoub, Haitham Elbardisi and Mohamed Arafa, Hamad General Hospital, Doha, Qatar; Dr. Ralf Henkel, University of the Western Cape, Bellville, South Africa; Dr. Juan Alvarez, La Coruna, Spain; Dr. Eva Tvrda, Slovak University of Agriculture, Nitra, Slovak Republic; and Dr. Manesh Kumar Panner Selvam, Tania R. Dias and Ana D. Martins, American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, Ohio. Dr. Belinda Willard, Director, Proteomic Core Laboratory, Lerner Research Institute, assisted with proteomic analysis. GeneGo provided MetaCore Pathway Maps and Disease Marker Sets.MetricsAuthor Information Luna Samanta American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio Redox Biology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Odisha, India More articles by this author Ashok Agarwal American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Nirlipta Swain American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio Redox Biology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University, Odisha, India More articles by this author Rakesh Sharma American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Banu Gopalan Yorg Corp., Plano, Texas More articles by this author Sandro C. Esteves ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, Brazil More articles by this author Damayanthi Durairajanayagam Discipline of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia More articles by this author Edmund Sabanegh Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Expand All Advertisement PDF downloadLoading ...