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NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE133742 | GEO | 2020/05/06

REPOSITORIES: GEO

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NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure.

Project description: Not available

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NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RRBS)

Project description:There is growing evidence that paternal pre-conception cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring. To characterize the effects of CS exposure on the sperm epigenome and offspring neurodevelopment, we investigated the impact of pre-conception paternal CS exposure on mouse sperm DNA methylation and gene expression in offspring. We further investigated the role of oxidative stress on sperm epigenetic changes using a mouse model (Nrf-/-) with impaired antioxidant capacity. Lastly, we evaluated the capacity for sperm DNA methylation to recover following removal of CS for 1-5 spermatogenic cycles (28-171 days). We found that smoking significantly impacts sperm DNA methylation as well as DNA methylation and gene expression in offspring. These changes were largely recapitulated in Nrf-/- mice independent of smoke exposure. Recovery experiments indicated that about half of differentially methylated regions returned to normal within 28 days of removal from smoke, however additional recovery following longer periods was not observed. Thus, we present strong evidence that cigarette smoke exposure induces paternally mediated, heritable epigenetic changes. Parallel studies performed in Nrf-/- mice provide evidence for oxidative stress as the predominant underlying mechanism for smoke-induced epigenetic changes to sperm as well as changes in the offspring of smoke-exposed sires. Lastly, recovery experiments indicate that while many epigenetic changes are corrected following removal from smoke exposure, aberrant methylation persists at a significant number of regions even after five spermatogenic cycles

2020-05-06 | GSE133739 | GEO

NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RNA-seq)

2020-05-06 | GSE133740 | GEO

NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure

Project description:NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure

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NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RRBS)

Project description:NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RRBS)

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NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RNA-seq)

Project description:NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RNA-seq)

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