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Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome

BACKGROUND: Environmental factors during perinatal development may influence developmental plasticity and disease susceptibility via alterations to the epigenome. Developmental exposure to the endocrine active compound, bisphenol A (BPA), has previously been associated with altered methylation at ca...

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Autores principales: Kim, Jung H, Sartor, Maureen A, Rozek, Laura S, Faulk, Christopher, Anderson, Olivia S, Jones, Tamara R, Nahar, Muna S, Dolinoy, Dana C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902427/
https://www.ncbi.nlm.nih.gov/pubmed/24433282
http://dx.doi.org/10.1186/1471-2164-15-30
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author Kim, Jung H
Sartor, Maureen A
Rozek, Laura S
Faulk, Christopher
Anderson, Olivia S
Jones, Tamara R
Nahar, Muna S
Dolinoy, Dana C
author_facet Kim, Jung H
Sartor, Maureen A
Rozek, Laura S
Faulk, Christopher
Anderson, Olivia S
Jones, Tamara R
Nahar, Muna S
Dolinoy, Dana C
author_sort Kim, Jung H
collection PubMed
description BACKGROUND: Environmental factors during perinatal development may influence developmental plasticity and disease susceptibility via alterations to the epigenome. Developmental exposure to the endocrine active compound, bisphenol A (BPA), has previously been associated with altered methylation at candidate gene loci. Here, we undertake the first genome-wide characterization of DNA methylation profiles in the liver of murine offspring exposed perinatally to multiple doses of BPA through the maternal diet. RESULTS: Using a tiered focusing approach, our strategy proceeds from unbiased broad DNA methylation analysis using methylation-based next generation sequencing technology to in-depth quantitative site-specific CpG methylation determination using the Sequenom EpiTYPER MassARRAY platform to profile liver DNA methylation patterns in offspring maternally exposed to BPA during gestation and lactation to doses ranging from 0 BPA/kg (Ctr), 50 μg BPA/kg (UG), or 50 mg BPA/kg (MG) diet (N = 4 per group). Genome-wide analyses indicate non-monotonic effects of DNA methylation patterns following perinatal exposure to BPA, corroborating previous studies using multiple doses of BPA with non-monotonic outcomes. We observed enrichment of regions of altered methylation (RAMs) within CpG island (CGI) shores, but little evidence of RAM enrichment in CGIs. An analysis of promoter regions identified several hundred novel BPA-associated methylation events, and methylation alterations in the Myh7b and Slc22a12 gene promoters were validated. Using the Comparative Toxicogenomics Database, a number of candidate genes that have previously been associated with BPA-related gene expression changes were identified, and gene set enrichment testing identified epigenetically dysregulated pathways involved in metabolism and stimulus response. CONCLUSIONS: In this study, non-monotonic dose dependent alterations in DNA methylation among BPA-exposed mouse liver samples and their relevant pathways were identified and validated. The comprehensive methylome map presented here provides candidate loci underlying the role of early BPA exposure and later in life health and disease status.
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spelling pubmed-39024272014-01-28 Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome Kim, Jung H Sartor, Maureen A Rozek, Laura S Faulk, Christopher Anderson, Olivia S Jones, Tamara R Nahar, Muna S Dolinoy, Dana C BMC Genomics Research Article BACKGROUND: Environmental factors during perinatal development may influence developmental plasticity and disease susceptibility via alterations to the epigenome. Developmental exposure to the endocrine active compound, bisphenol A (BPA), has previously been associated with altered methylation at candidate gene loci. Here, we undertake the first genome-wide characterization of DNA methylation profiles in the liver of murine offspring exposed perinatally to multiple doses of BPA through the maternal diet. RESULTS: Using a tiered focusing approach, our strategy proceeds from unbiased broad DNA methylation analysis using methylation-based next generation sequencing technology to in-depth quantitative site-specific CpG methylation determination using the Sequenom EpiTYPER MassARRAY platform to profile liver DNA methylation patterns in offspring maternally exposed to BPA during gestation and lactation to doses ranging from 0 BPA/kg (Ctr), 50 μg BPA/kg (UG), or 50 mg BPA/kg (MG) diet (N = 4 per group). Genome-wide analyses indicate non-monotonic effects of DNA methylation patterns following perinatal exposure to BPA, corroborating previous studies using multiple doses of BPA with non-monotonic outcomes. We observed enrichment of regions of altered methylation (RAMs) within CpG island (CGI) shores, but little evidence of RAM enrichment in CGIs. An analysis of promoter regions identified several hundred novel BPA-associated methylation events, and methylation alterations in the Myh7b and Slc22a12 gene promoters were validated. Using the Comparative Toxicogenomics Database, a number of candidate genes that have previously been associated with BPA-related gene expression changes were identified, and gene set enrichment testing identified epigenetically dysregulated pathways involved in metabolism and stimulus response. CONCLUSIONS: In this study, non-monotonic dose dependent alterations in DNA methylation among BPA-exposed mouse liver samples and their relevant pathways were identified and validated. The comprehensive methylome map presented here provides candidate loci underlying the role of early BPA exposure and later in life health and disease status. BioMed Central 2014-01-17 /pmc/articles/PMC3902427/ /pubmed/24433282 http://dx.doi.org/10.1186/1471-2164-15-30 Text en Copyright © 2014 Kim et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kim, Jung H
Sartor, Maureen A
Rozek, Laura S
Faulk, Christopher
Anderson, Olivia S
Jones, Tamara R
Nahar, Muna S
Dolinoy, Dana C
Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome
title Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome
title_full Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome
title_fullStr Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome
title_full_unstemmed Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome
title_short Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome
title_sort perinatal bisphenol a exposure promotes dose-dependent alterations of the mouse methylome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902427/
https://www.ncbi.nlm.nih.gov/pubmed/24433282
http://dx.doi.org/10.1186/1471-2164-15-30
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