Perinatal exposure to lead and DEHP change DNA methylation profile in mouse liver and blood
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ABSTRACT:
PROVIDER: PRJNA633133 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11798000.fastq.gz | Fastqsanger.gz | |||
| SRR11798100.fastq.gz | Fastqsanger.gz | |||
| SRR11798001.fastq.gz | Fastqsanger.gz | |||
| SRR11798101.fastq.gz | Fastqsanger.gz | |||
| SRR11798002.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Then goal of this study id to investigate the effects of perinatal lead (32 ppm in maternal drinking water) and DEHP (25 mg per kg of chow) exposure on liver and blood DNA methylation in both PND21 and 5-month male and female mice. Methods: Enhanced reduced-representation bisulfite sequencing (ERRBS) was used to assess DNA methylation in PND21 and 5-month old DEHP-exposed, lead-exposed and control mice. Sex-specific differential methylaton analysis by DEHP and lead exposure was conducted using MethylSig R package. Results: We observed hundreds to thousands of stably modified, sex-specific differentially methylated regions in blood and liver of DEHP-exposed and lead-exposed animals at both PND21 and 5 months.
2020-07-01 | GSE150670 | GEO
Project description:The developing epigenome changes rapidly, potentially making it more sensitive to toxicant exposures. DNA modifications, including methylation and hydroxymethylation, are important parts of the epigenome that may be affected by environmental exposures. However, most studies do not differentiate between these two DNA modifications, possibly masking significant effects. To investigate the relationship between DNA hydroxymethylation and developmental exposure to common contaminants, a collaborative, NIEHS-sponsored consortium, TaRGET II, initiated longitudinal mouse studies of developmental exposure to human-relevant levels of the phthalate plasticizer di(2-ethylhexyl) phthalate (DEHP), and the metal lead (Pb). Exposures to 25 mg DEHP/kg of food (approximately 5 mg DEHP/kg body weight) or 32 ppm Pb-acetate in drinking water were administered to nulliparous adult female mice. Exposure began 2 weeks before breeding, and continued throughout pregnancy and lactation, until offspring were 21 days old. At 5 months, perinatally exposed offspring blood and cortex tissue were collected, for a total of 25 male mice and 17 female mice (n=5-7 per tissue and exposure). DNA was extracted and hydroxymethylation was measured using hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq). Differential peak and pathway analysis was conducted comparing across exposure groups, tissue types, and animal sex, using an FDR cutoff of 0.15. DEHP-exposed females had two genomic regions with lower hydroxymethylation in blood and no differences in cortex hydroxymethylation. For DEHP-exposed males, ten regions in blood (six higher and four lower) and 246 regions (242 higher and four lower) and four pathways in cortex were identified. Pb-exposed females had no statistically significant differences in blood or cortex hydroxymethylation compared to controls. Pb-exposed males, however, had 385 regions (all higher) and six pathways altered in cortex, but no differential hydroxymethylation was identified in blood. Overall, perinatal exposure to human-relevant levels of two common toxicants showed differences in DNA hydroxymethylation specific to sex, exposure type, and tissue, but male cortex was most susceptible to hydroxymethylation differences by exposure. Future assessments should focus on understanding if these findings indicate potential biomarkers of exposure or are related to functional long-term health effects.
2023-04-28 | GSE229717 | GEO
Project description:Brain and Blood Hydroxymethylation in Mice after Lead (Pb) and DEHP Exposure
| PRJNA955690 | ENA
Project description:In this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45), across three strains (Fischer, Long Evans and Sprague Dawley). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 119) Gene expression was profiled in the hippocampus of rats at no lead exposure (0ppm), 250ppm and 750 ppm lead exposure levels during perinatal and postnatal developmental periods of both males and females of three strains of rat (Fischer, Long Evans and Sprague Dawley).
2014-04-10 | E-GEOD-56666 | biostudies-arrayexpress
Project description:In this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 40) Gene expression was profiled in hippocampus at no lead exposure (0ppm), 250ppm and 750 ppm lead exposure level at peinatal and postnaltal developmental period.
2012-05-30 | E-GEOD-38348 | biostudies-arrayexpress
Project description:DEHP study Phthalate plasticizers are ubiquitous chemicals linked to several cardiovascular diseases in animal models and in humans. In spite of this, the mechanisms by which phthalate exposures cause adverse cardiac health outcomes are unclear. In particular, whether phthalate exposures during pregnancy interfere with normal developmental programming of the cardiovascular system, and the resulting implications this may have for long-term disease risk, are unknown. Recent studies suggest that the effects of phthalates on metabolic and neurobehavioral outcomes are sex-specific. However, the influence of sex on cardiac susceptibility to phthalate exposures has not been investigated. One mechanism by which developmental exposures may influence long-term health is through altered programming of DNA methylation. In this work, we utilized an established mouse model of human-relevant perinatal exposure and enhanced reduced representation bisulfite sequencing to investigate the long-term effects of diethylhexyl phthalate (DEHP) exposure on DNA methylation in the hearts of adult male and female offspring at 5 months of age (n=5-7 mice per sex and exposure). Perinatal DEHP exposure led to hundreds of sex-specific, differentially methylated cytosines (DMCs) and differentially methylated regions (DMRs) in the heart. Pathway analysis of DMCs revealed enrichment for several pathways in females, including insulin signaling, regulation of histone methylation, and tyrosine phosphatase activity. In males, DMCs were enriched for glucose transport, energy generation, and developmental programs. Notably many sex-specific genes differentially methylated with DEHP exposure in our mouse model were also differentially methylated in published data of heart tissues collected from human heart failure patients. Together these data highlight the potential role for DNA methylation in DEHP-induced cardiac effects, and emphasize the importance of sex as a biological variable in environmental health studies. Lead study Environmental factors play an important role in the etiology of cardiovascular diseases. Cardiovascular diseases exhibit marked sexual dimorphism; however, the sex-specific effects of environmental exposures on cardiac health are incompletely understood. Perinatal and adult exposures to the metal lead (Pb) are linked to several adverse cardiovascular outcomes, but the sex-specific effects of this toxicant on the heart have received little attention. Perinatal environmental exposures can lead to disease through disruption of the normal epigenetic programming that occurs during early development. Using a mouse model of human-relevant perinatal environmental exposure, we investigated the effects of exposure to Pb during gestation and lactation on DNA methylation in the hearts of adult offspring mice (n=6 per sex). Two weeks prior to mating, dams were assigned to control or Pb acetate (32 ppm) water, and exposure continued until offspring were weaned at 3 weeks of age. Enhanced reduced-representation bisulfite sequencing was used to measure DNA methylation in the hearts of offspring at 5 months of age. Although Pb exposure stopped at 3 weeks of age, we discovered hundreds of differentially methylated cytosines (DMCs) and regions (DMRs) in males and females at 5 months of age. DMCs/DMRs and their associated genes were sex-specific, with a small, but statistically significant subset overlapping between sexes. Pathway analysis revealed altered methylation of genes important for cardiac and other tissue development in males, and histone demethylation in females. Together, these data demonstrate that perinatal exposure to Pb induces sex-specific changes in cardiac DNA methylation that are present long after cessation of exposure, and highlight the importance of considering sex in environmental epigenetics and mechanistic toxicology studies.
2020-07-15 | GSE152711 | GEO
Project description:We investigated the impact of prenatal exposure to DEHP on spermatogenesis and DNA sperm methylation in F1 mice strains FVB/N and C57BL/6J. Prenatal exposition was performed orally on mothers with 300 mg/kg/day of DEHP from gestation day 9 to 19. 20 sperm-extracted DNA samples of males born from DEHP-treated and control mothers were analysed by MBD-seq at NXT-DX company.
2015-03-24 | GSE67159 | GEO
Project description:In this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 40)
2012-05-31 | GSE38348 | GEO
Project description:BACKGROUND: Phthalates are manmade industrial additives used mostly as plasticizers. In addition to their deleterious effects on male genital development, population studies have recently documented correlations between phthalates exposure and subtle impacts on reproductive tract development and on the metabolic syndrome in male adults. In mature rodents liver di-(2-ethylhexyl)-phthalate (DEHP) activates the peroxisome proliferators-activated receptor (PPARalpha), a member of the nuclear receptor (NR) superfamily. OBJECTIVES: Using a systems biology approach, we aimed at defining potential mechanisms underlying the impacts of DEHP on adult mouse liver and testis. METHODS: Thus, we performed a parallel analysis of transcript and metabolic profiles in the liver from adult mice exposed to varying DEHP doses. Moreover, we obtained pangenomic mRNA profiles of laser-captured Leydig and Sertoli cells from mature animals exposed to DEHP. RESULTS: Hepatic genes modulated by DEHP are predominantly PPARalpha targets. However, the induction of some prototypic cytochrome P450 genes strongly supports the activation of additional NR pathways. Integration of hepatic transcriptomic and metabonomic profiles further revealed a correlation between the impacts of DEHP on a cluster of genes and metabolites linked to heme synthesis and on a cluster of Rev-erbalpha target genes related to metabolic and circadian clock pathways. Cell-specific effects of DEHP were investigated in the adult testis and a noticeable impact of DEHP was observed on Leydig cells transcriptome. CONCLUSIONS: We report a detailed analysis of DEHP interference with hepatic Constitutive Androstane Receptor (CAR) and Rev-erbalpha pathways and a novel transcriptional impact of DEHP on adult endocrine cells of the testis. Keywords: Treatment effect
2009-02-19 | GSE13240 | GEO
Project description:In this study we analyzed the effects of lead-exposure up hippocampal gene expression in males and females exposed to 0ppm, 250ppm and 750ppm lead during two different developmental periods, perinatal (in utero through to weaning at PND21) and postnatal (PND0-PND45), across three strains (Fischer, Long Evans and Sprague Dawley). All tissue was taken at PND 55. We used affymetrix Rat Gene 1.0ST arrays to obtain global gene expression data from each animal, with a group size of 4 for all conditions (Total number of Arrays = 119)
2014-04-10 | GSE56666 | GEO