Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Whole genome bisulfite sequencing of nicotine-exposed sperm reveals differences in global DNA methylation levels, which would partially reverse following cessation

ABSTRACT: DNA methylation, a pivotal epigenetic modification, regulates the expression of numerous genes during spermatogenesis and influences health outcomes in offspring. We have conducted whole genome bisulfite sequencing (WGBS) to explore the effects of nicotine exposure on global sperm DNA methylation patterns. Previous studies have shown that nicotine exposure increased DNA methylation status in sperm, whereas the detailed mapping of global DNA methylation patterns remains elusive. In addition, whether the DNA methylation changes induced by nicotine may be reversible upon cessation is still unclear. Here, we demonstrated the effects of nicotine exposure on global sperm DNA methylation patterns and verified the reversibility of this phenomenon, providing new insights into the mechanisms by which smoking affects male fertility and the long-term health of offspring.

ORGANISM(S): Mus musculus

PROVIDER: GSE284004 | GEO | 2025/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Cigarette smoking significantly alters sperm DNA methylation patterns

Project description:Numerous health consequences of tobacco smoke exposure have been characterized, and the effects of smoking on traditional measures of male fertility are well described. However, a growing body of data indicates that pre‐conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through spermatozoa. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never‐smokers using the Infinium Human Methylation 450 beadchip. We investigated two models of DNA methylation alterations: (i) consistently altered methylation at specific CpGs or within specific genomic regions and (ii) stochastic DNA methylation alterations manifest as increased variability in genome‐wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome‐wide in sperm DNA from men who smoke compared with never‐smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre‐conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.

2018-05-23 | GSE114753 | GEO

Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring [Bisulfite-seq]

Project description:We tested the effects of chronic paternal nicotine exposure in C57BL6/J mice on hippocampal DNA methylation in F1 offspring.

2019-11-25 | GSE140904 | GEO

Cold exposure impacts DNA methylation patterns in cattle sperm

Project description:Epigenetic markers, such as DNA methylation, in sperm plays crucial roles in spermatogenesis and fertilization, and a portion of methylation escape the early embryonic genome-wide DNA demethylation and affect later growth and development of offspring. DNA methylation is influenced by various exogenous factors such as nutrition, temperature, toxicants, and stress. The effects of this cold exposure on the methylation dynamics of bovine sperm remain unexamined. Methylation profiles of sperm, collected from bulls during summer and winter seasons were analyzed by Whole Genome Bisulfite Sequencing (WGBS). Cold exposure during winter does not have a significant effect on the global methylation level, it altered the methylation levels at certain genomic loci and genes that may impact the maintenance of methylation status of imprinted genes and other loci, which may impact the development and growth of offspring.

2024-01-31 | GSE222863 | GEO

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

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

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

2020-05-06 | GSE133739 | GEO

Perinatal exposure to nicotine alters spermatozoal DNA methylation near genes controlling nicotine action

Project description:Perinatal smoke/nicotine exposure alters lung development and causes asthma in exposed offspring, transmitted transgenerationally. The mechanism underlying the transgenerational inheritance of perinatal smoke/nicotine-induced asthma remains unknown, but germline epigenetic modulations may play a role. Using a well-established rat model of perinatal nicotine-induced asthma, we determined the DNA methylation pattern of spermatozoa of F1 rats exposed perinatally to nicotine in F0 gestation. To identify differentially methylated regions (DMRs), reduced representation bisulfite sequencing was performed on spermatozoa of F1 litters. The top regulated gene body and promoter DMRs were tested for lung gene expression levels, and key proteins involved in lung development and repair were determined. The overall CpG methylation in F1 sperms across gene bodies, promoters, 5’UTRs, exons, introns, and 3’UTRs was not affected by nicotine exposure. However, the methylation levels were different between the different genomic regions. 81 CpG sites, 16 gene bodies, and 3 promoter regions were differentially methylated. Gene enrichment analysis of DMRs revealed pathways involved in oxidative stress, nicotine response, alveolar and brain development, and cellular signaling. Among the DMRs, Dio1 and Nmu were the most hypermethylated and hypomethylated genes, respectively. Gene expression analysis showed that the mRNA expression and DNA methylation were incongruous. Key proteins involved in lung development and repair were significantly different (FDR < 0.05) between the nicotine and placebo-treated groups. Our data show that DNA methylation is remodeled in offspring spermatozoa upon perinatal nicotine exposure. These epigenetic alterations may play a role in transgenerational inheritance of perinatal smoke/nicotine induced asthma.

2021-05-17 | GSE173898 | GEO

Effects of paternal nicotine taking on gene expression in dorsal hippocampus of drug naïve male offspring

Project description:Nicotine intake, whether through tobacco smoking or e-cigarettes, remains a global health concern. An emerging preclinical literature indicates that parental nicotine exposure produces behavioral, physiological, and molecular changes in subsequent generations. However, the heritable effects of voluntary parental nicotine taking are unknown. Here, we show increased acquisition of nicotine taking in male and female offspring of sires that self-administered nicotine. In contrast, self-administration of sucrose and cocaine were unaltered in male and female offspring suggesting that the intergenerational effects of paternal nicotine taking may be reinforcer specific. Further characterization revealed memory deficits and increased anxiety-like behaviors in drug-naïve male, but not female, offspring of nicotine-experienced sires. Using an unbiased, genome-wide approach, we discovered that these phenotypes were associated with decreased expression of Satb2, a transcription factor known to play important roles in synaptic plasticity and memory formation, in the hippocampus of nicotine-sired male offspring. This effect was sex-specific as no changes in Satb2 expression were found in nicotine-sired female offspring. Finally, increasing Satb2 levels in the hippocampus prevented the escalation of nicotine intake and rescued the memory deficits associated with paternal nicotine taking in male offspring. Collectively, these findings indicate that paternal nicotine taking produces heritable sex-specific molecular changes that promote addiction-like phenotypes and memory impairments in male offspring. To characterize the molecular changes associated with the heritable effects of paternal nicotine taking, an unbiased, whole-genome analysis was used to characterize the hippocampal transcriptome of drug-naïve F1 males

2022-04-01 | GSE199661 | GEO

Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals (MeDIP-Seq)

Project description:The global prevalence of type 2 diabetes (T2D) is increasing, and it is contributing to the susceptibility to diabetes and its related epidemic in offspring. Although the impacts of paternal T2D on metabolism of offspring have been well established, the exact molecular and mechanistic basis that mediates these impacts remains largely unclear. Here we show that paternal T2D increases the susceptibility to diabetes in offspring through the gametic epigenetic alterations. Paternal T2D led to glucose intolerance and insulin resistance in offspring. Relative to controls, offspring of T2D fathers exhibited altered gene expression patterns in the pancreatic islets, with downregulation of several genes involved in glucose metabolism and insulin signaling pathway. Epigenomic profiling of offspring pancreatic islets revealed numerous changes in cytosine methylation depending on paternal T2D, including reproducible changes in methylation over several insulin signaling genes. Paternal T2D altered overall methylome patterns in sperm, with a large portion of differentially methylated genes overlapped with that of pancreatic islets in offspring. Our study revealed, for the first time, that T2D can be inherited transgenerationally through the mammalian germline by an epigenetic manner. Examination of the effect of paternal T2D on the DNA methylation in the pancreatic islets of offspring and in the sperm of father.

2013-01-02 | E-GEOD-43238 | biostudies-arrayexpress

Gene expression in the mouse embryo following early pregnancy exposure to ethanol or nicotine

Project description:The in utero environment is a critical determinant of the immediate and future health of the developing fetus. Two of the most commonly used drugs during pregnancy are alcohol and nicotine. While prolonged gestational exposure to alcohol or nicotine has been associated with a range of adverse outcomes in the offspring, the consequences of exposure during early gestation only are less well understood. Here, we use mouse models of relatively moderate early gestational ethanol or nicotine exposure to profile gene expression in whole male embryos at 9.5 days post coitum using an Illumina microarray.

2021-08-18 | GSE94347 | GEO

Cold exposure impacts DNA methylation patterns in cattle sperm

Project description:Cold exposure impacts DNA methylation patterns in cattle sperm

| PRJNA923667 | ENA