Luna Samanta1, Ashok Agarwal2, Nirlipta Swain1, Rakesh Sharma3, Banu Gopalan4, Sandro C Esteves5, Damayanthi Durairajanayagam6, Edmund Sabanegh7. 1. 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. 2. American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio. Electronic address: agarwaa@ccf.org. 3. American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio. 4. Yorg Corp., Plano, Texas. 5. ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, Brazil. 6. Discipline of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia. 7. Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio.
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.
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.
Authors: María José Gómez-Torres; Natalia Huerta-Retamal; Paula Sáez-Espinosa; Laura Robles-Gómez; Manuel Avilés; Jon Aizpurua Journal: Reprod Sci Date: 2022-07-11 Impact factor: 2.924
Authors: Ashok Agarwal; Neel Parekh; Manesh Kumar Panner Selvam; Ralf Henkel; Rupin Shah; Sheryl T Homa; Ranjith Ramasamy; Edmund Ko; Kelton Tremellen; Sandro Esteves; Ahmad Majzoub; Juan G Alvarez; David K Gardner; Channa N Jayasena; Jonathan W Ramsay; Chak Lam Cho; Ramadan Saleh; Denny Sakkas; James M Hotaling; Scott D Lundy; Sarah Vij; Joel Marmar; Jaime Gosalvez; Edmund Sabanegh; Hyun Jun Park; Armand Zini; Parviz Kavoussi; Sava Micic; Ryan Smith; Gian Maria Busetto; Mustafa Emre Bakırcıoğlu; Gerhard Haidl; Giancarlo Balercia; Nicolás Garrido Puchalt; Moncef Ben-Khalifa; Nicholas Tadros; Jackson Kirkman-Browne; Sergey Moskovtsev; Xuefeng Huang; Edson Borges; Daniel Franken; Natan Bar-Chama; Yoshiharu Morimoto; Kazuhisa Tomita; Vasan Satya Srini; Willem Ombelet; Elisabetta Baldi; Monica Muratori; Yasushi Yumura; Sandro La Vignera; Raghavender Kosgi; Marlon P Martinez; Donald P Evenson; Daniel Suslik Zylbersztejn; Matheus Roque; Marcello Cocuzza; Marcelo Vieira; Assaf Ben-Meir; Raoul Orvieto; Eliahu Levitas; Amir Wiser; Mohamed Arafa; Vineet Malhotra; Sijo Joseph Parekattil; Haitham Elbardisi; Luiz Carvalho; Rima Dada; Christophe Sifer; Pankaj Talwar; Ahmet Gudeloglu; Ahmed M A Mahmoud; Khaled Terras; Chadi Yazbeck; Bojanic Nebojsa; Damayanthi Durairajanayagam; Ajina Mounir; Linda G Kahn; Saradha Baskaran; Rishma Dhillon Pai; Donatella Paoli; Kristian Leisegang; Mohamed Reza Moein; Sonia Malik; Onder Yaman; Luna Samanta; Fouad Bayane; Sunil K Jindal; Muammer Kendirci; Baris Altay; Dragoljub Perovic; Avi Harlev Journal: World J Mens Health Date: 2019-05-28 Impact factor: 5.400
Authors: Ashok Agarwal; Manesh Kumar Panner Selvam; Luna Samanta; Sarah C Vij; Neel Parekh; Edmund Sabanegh; Nicholas N Tadros; Mohamed Arafa; Rakesh Sharma Journal: Antioxidants (Basel) Date: 2019-10-16