NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure
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ABSTRACT:
PROVIDER: PRJNA552363 | ENA |
REPOSITORIES: ENA
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Project description:NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RRBS)
| PRJNA552369 | ENA
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
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 | GSE133740 | GEO
Project description:NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure (RNA-seq)
| PRJNA552368 | ENA
Project description: Not available
| S-EPMC7307791 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-05-06 | GSE133742 | GEO
Project description:To investigate whether paternal tobacco smoke (PTS) was associated with prenatal epigenetic programming of CG site methylation, 20 cord blood DNA samples from newborns with and without PTS were subjected to microarray assay of 1,505 CG loci in 807 genes by Illumina GoldenGate® technology bead system to obtain high-throughput DNA Methylation profiles. Samples included 14 newborns without PTS exposure, and 6 newborns with PTS exposure.
2019-04-13 | GSE129751 | GEO
Project description:Kentucky assay: cigarette smoke
| PRJNA626542 | ENA
Project description:Cigarette smoke (CS) imposes a strong oxidative burden on exposed tissues resulting in a severely disturbed oxidant/antioxidant balance, which in the context of chronic exposure is assumed to be a key contributor to CS-related diseases. Because of its emerging central role in orchestrating the general cellular antioxidant response, the pathway leading to the activation of the transcription factor Nrf2 has received mounting attention over the past decade in investigations aimed at elucidating CS-induced patho-physiological mechanisms. To comprehensively characterize the impact of Nrf2 in acute and sub-chronic smoking scenarios, Nrf2 knock-out mice and their wildtype ICR littermates were exposed to either ambient air (sham exposure) or to one of three doses of CS for up to 5 months with two post-exposure endpoints of 1 and 13 days. The lungs of the mice were monitored for transcriptomic changes on a genome-wide level. 110 samples from 28 different groups are analyzed. For each group there are 4 replicates, besides two groups with only 3 replicates. Group parameteres are: genotype (WT, KN), treatment (sham, smoke), dosage of smoke treatment (low, medium, high), time of smoke treatment (1 day, 2 month, 5 month, 5 month + 1 day recovery, 5 month + 13 days recovery)
2010-02-27 | E-GEOD-18344 | biostudies-arrayexpress
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