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

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

PROVIDER: PRJNA552368 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9636900.fastq.gz	Fastqsanger.gz
	SRR9636910.fastq.gz	Fastqsanger.gz
	SRR9636920.fastq.gz	Fastqsanger.gz
	SRR9636901.fastq.gz	Fastqsanger.gz
	SRR9636911.fastq.gz	Fastqsanger.gz

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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 (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:Paternal cigarette smoke (CS) exposure is associated with increased risk of behavioral disorders and cancer in offspring, but the mechanism has not been identified. Here we use mouse models to investigate mechanisms and impacts of paternal 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 is associated with changes in prefrontal cortex DNAme and gene expression patterns in offspring. Remarkably, the epigenetic and transcriptional effects of CS exposure that we observed in wild type mice are partially recapitulated in Nrf2-/- mice and their offspring, independent of smoking status. Nrf2 is a central regulator of antioxidant gene transcription, and mice lacking Nrf2 consequently display elevated oxidative stress, suggesting that oxidative stress may underlie CS-induced heritable epigenetic changes. Importantly, paternal sperm DNAme changes do not overlap with DNAme changes measured in offspring prefrontal cortex, indicating that the observed DNAme changes in sperm are not directly inherited. Additionally, the changes in sperm DNAme associated with CS exposure were not observed in sperm of unexposed offspring, suggesting the effects are likely not maintained across multiple generations.

| S-EPMC7307791 | biostudies-literature

NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-05-06 | GSE133742 | GEO

NHBE exposed to cigarette smoke

Project description:normal human bronchial epithelial cultures from two cultures in parallel exposed to cigarette smoke (CS) or air (mock) at timepoints 4 hours and 24 hours. Keywords = cigarette smoke Keywords = microarray Keywords = bronchial cell Keywords = tobacco Keywords: time-course

2005-02-23 | GSE2302 | GEO

Kentucky assay: cigarette smoke

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Transcriptional response of Mycobacterium tuberculosis to cigarette smoke condensate

Project description:Mycbacterium tuberculosis was exposed to cigarette smoke condensate (CSC) in 7H9 dextrose culture media. The transcriptional response to cigarette smoke condensate was compared to that of exposure to the CSC diluent, DMSO..

2021-04-15 | GSE172041 | GEO

mouse lung resistance or sensitivity to cigarette smoke

Project description:We have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57Bl/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, while ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype.

2008-07-10 | GSE12036 | GEO

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