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Status |
Public on Oct 24, 2016 |
Title |
Preferential Epigenetic Programming of Estrogen Response after in utero xenoestrogen (bisphenol-A) exposure [NimbleGen] |
Organism |
Mus musculus |
Experiment type |
Methylation profiling by genome tiling array
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Summary |
Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure toBPAin utero hasbeen linked tofemale reproductive disorders, including endometrial hyperplasiaandbreast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the globalCpGmethylation pattern of the uterine genome, subsequent gene expression, and estrogen response.Pregnantmicewere exposed to an environmentally relevant dose of BPAorDMSOcontrol.Uterine DNAand RNAwere examined by usingmethylatedDNAimmunoprecipitationmethylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-a (ERa)–binding genes. The majority of genes that demonstrated both altered expression and ERa binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERa. Gene– environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogenrelateddisease in adults.—Jorgensen, E. M.,Alderman,M.H., III,Taylor, H. S. Preferential epigenetic programmingof estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
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Overall design |
Dams were exposed to 5 mg/kg/day BPA or DMSO control for day 9-21 of pregnancy. Offspring were euthenized at 2 weeks and their uteri harvested. Samples are pooled by litter.
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Contributor(s) |
Jorgensen EM, Alderman III MH, Taylor HS |
Citation(s) |
27312807 |
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Submission date |
Oct 24, 2016 |
Last update date |
Oct 24, 2016 |
Contact name |
Myles H Alderman III |
Organization name |
Yale University School of Medicine
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Department |
Cell Biology
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Street address |
10 Amistad St
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City |
New Haven |
State/province |
Ct |
ZIP/Postal code |
06519 |
Country |
USA |
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Platforms (1) |
GPL18163 |
NimbleGen Mouse DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Array [090618_MM9_CpG_Refseq_Prom_MeDIP] |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE89131 |
Preferential Epigenetic Programming of Estrogen Response after in utero xenoestrogen (bisphenol-A) exposure |
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Relations |
BioProject |
PRJNA350332 |