Oxidative stress underlies heritable impacts of paternal cigarette smoke exposure
| Autor: | Jingtao Guo, Kenneth I. Aston, Thomas P. Huecksteadt, Emma R. James, James M. Hotaling, David Alonso, Patrick J. Murphy, Timothy G. Jenkins, D.T. Carrell, Brad R. Cairns, Hoidal, Dallin S. Broberg |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
030219 obstetrics & reproductive medicine Offspring Methylation Oxidative phosphorylation Biology medicine.disease_cause Phenotype Sperm Andrology 03 medical and health sciences 0302 clinical medicine Gene expression medicine sense organs Epigenetics Oxidative stress 030304 developmental biology |
| DOI: | 10.1101/750638 |
| Popis: | SUMMARYPaternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. This study used mouse models to evaluate: 1) what impact paternal CS exposure has on sperm DNA methylation (DNAme), 2) whether sperm DNAme changes persist after CS exposure ends, 3) the degree to which DNAme and gene expression changes occur in offspring and 4) the mechanism underlying impacts of CS exposure. We demonstrate that CS exposure induces sperm DNAme changes that are partially corrected within 28 days of removal from CS exposure. Additionally, paternal smoking causes changes in neural DNAme and gene expression in offspring. Remarkably, the effects of CS exposure are largely recapitulated in oxidative stress-compromisedNrf2-/-mice and their offspring, independent of paternal smoking. These results demonstrate that paternal CS exposure impacts offspring phenotype and that oxidative stress underlies CS induced heritable epigenetic changes. |
| Databáze: | OpenAIRE |
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