Cocaine alters the mouse testicular epigenome with direct impact on histone acetylation and DNA methylation marks
| Autor: | Betina González, Candela Rocio Gonzalez, Veronica Bisagno, Camilo R. Gambini Pantoja, Máximo Hernán Sosa, Alfredo Daniel Vitullo |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Biology Epigenesis Genetic Ciencias Biológicas Histones 03 medical and health sciences Mice Cocaine Dopamine Uptake Inhibitors HDAC Testis Animals Epigenetics DNA METHYLATION EPIGENETIC GERM CELLS Obstetrics and Gynecology Acetylation Epigenome DNA Methylation Molecular biology Spermatozoa 030104 developmental biology Histone Reproductive Medicine HISTONE ACETYLATION DNA methylation biology.protein COCAINE Biología Reproductiva CIENCIAS NATURALES Y EXACTAS Developmental Biology |
| Zdroj: | Reproductive biomedicine online. 37(3) |
| ISSN: | 1472-6491 |
| Popis: | Research question: Recent evidence suggests that cocaine administration in animal models can trigger non-genetic inheritance of addiction traits from father to offspring, affecting development and behaviour. Is chronic cocaine intake involved in alterations of epigenetic homeostasis in the testis? Design: Epigenetic marks and mediators in testis and isolated germ cells of adult mice treated with cocaine (10 mg/kg) or vehicle (sterile saline solution) were evaluated in an intermittent binge protocol: three intraperitoneal injections, 1 h apart, one day on/off for 13 days, collecting tissue 24 h after the last binge administration (day 14). Results: It was shown that chronic cocaine intake in mice disrupts testicular epigenetic homeostasis, increasing global methylated cytosine levels in DNA from germ cells and sperm. Cocaine also increased testicular and germ cell acetylated histone 3 and 4 and decreased expression of histone deacetylases HDAC1/2. Immunolocalization studies showed that HDAC1/2 and acetylated histone 3 and 4 proteins localize to meiotic germ cells. Analysis of mRNA expression in isolated germ cells shows decreased levels of Hdac1/2/8, Dnmt3b and Tet1 and increased levels of Dnmt3a gene expression after cocaine treatment. Conclusions: Cocaine intake is associated with testicular toxicity and significant reproductive function impairment. The results presented here broaden the basic knowledge of the impact of addictive stimulants on testicular pathophysiology, fertility and male reproductive health and imply that altered epigenetic homeostasis by cocaine may have potential consequences on future generations. Fil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Pantoja, Camilo R. Gambini. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Sosa, Máximo Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Vitullo, Alfredo Daniel. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; Argentina Fil: Gonzalez, Candela Rocio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina |
| Databáze: | OpenAIRE |
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