Epigenetic dimension of oxygen radical injury in spermatogonial epithelial cells |
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| Institution: | 1. Translational Research Lab, School of Biological Sciences, Dr. H.S. Gour Central University, Sagar, India;2. Division of Translational Research, Tata Memorial Centre, ACTREC, Navi Mumbai, India;1. University of Melbourne, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, 250 Princes Highway, Werribee, VIC 3030, Australia;2. Redefining Agriculture Pty Ltd, PO Box 723, Brunswick Lower, VIC 3056, Australia;3. Jemora Pty Ltd., PO Box 2277, Geelong 3220, VIC, Australia;4. Mackinnon Project, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, 250 Princes Highway, Werribee, VIC 3030, Australia;1. WIL Research Laboratories, Ashland, OH, United States;2. Ashland, OH, United States;3. University of Michigan, Ann Arbor, MI, United States;4. Biologics Consulting Group, Alexandria, VA, United States;5. SNBL USA, Everett, WA, United States;6. Exponent, Inc., Alexandria, VA, United States;7. Georgetown University School of Medicine, Washington, DC, United States;1. Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias, Instituto Nacional de Tecnología Agropecuaria (INTA)-Castelar, Buenos Aires, Argentina;2. Laboratorio de Inmunología, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina;3. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina;1. State Key Laboratory of Bioreactor Engineering, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China;2. Qinghai Academy of Veterinary Medicine and Animal Science, Xining 810016, China;3. Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA;1. Ashland, OH, United States;2. WIL Research Laboratories, Ashland, OH, United States;3. Biologics Consulting Group, Alexandria, VA, United States;4. SNBL USA, Everett, WA, United States;5. Exponent, Inc., Alexandria, VA, United States;6. Georgetown University School of Medicine, Washington, DC, United States |
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| Abstract: | The present work reports a direct role of mitochondrial oxidative stress induced aberrant chromatin regulation, as a central phenomenon, to perturbed genomic integrity in the testicular milieu. Oxygen-radical injury following N-succinimidyl N-methylcarbamate treatment in mouse spermatogonial epithelial (GC-1 spg) cells induced functional derailment of mitochondrial machinery. Mitophagy resulted in marked inhibition of mitochondrial respiration and reduced mtDNA copy number. Impaired cell cycle progression along with altered H3K9me1, H4K20me3, H3, AcH3 and uH2A histone modifications were observed in the treated cells. Dense heterochromatin foci and aberrant expression of HP1α in nuclei of treated cells implied onset of senescence associated secretory phenotype mediated through nuclear accumulation of NF-κB. Neoplastic nature of daughter clones, emerged from senescent mother phenotypes was confirmed by cytogenetic instability, aberrant let-7a and let-7b miRNA expression and anchorage independent growth. Together, our results provide the first insights of redox-dependent epigenomic imbalance in spermatogonia, a previously unknown molecular paradigm. |
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| Keywords: | Mitochondria Histone modifications DNA methylation miRNA Senescence Isocyanate toxicity |
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