Journal article
Novel Epigenetic Biomarkers Mediating Bisphenol A Exposure and Metabolic Phenotypes in Female Mice
Endocrinology (Philadelphia), v 158(1), pp 31-40
01 Jan 2017
PMID: 27824486
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
There is compelling evidence that epigenetic modifications link developmental environmental insults to adult disease susceptibility. Animal studies have associated perinatal bisphenol A (BPA) exposure to altered DNA methylation, but these studies are often limited to candidate gene and global non-loci-specific approaches. By using an epigenome-wide discovery platform, we elucidated epigenetic alterations in liver tissue from adult mice offspring (10 months) following perinatal BPA exposure at human physiologically relevant doses (50-ng, 50-μg, and 50-mg BPA/kg diet). Biological pathway analysis identified an enrichment of significant differentially methylated regions in metabolic pathways among females. Furthermore, through the use of top enriched biological pathways, 4 candidate genes were chosen to assess DNA methylation as a mediating factor linking the association of perinatal BPA exposure to metabolic phenotypes previously observed in female offspring. DNA methylation status at Janus kinase-2 (Jak-2), retinoid X receptor (Rxr), regulatory factor x-associated protein (Rfxap), and transmembrane protein 238 (Tmem238) was used within a mediational regression analysis. DNA methylation in all four of the candidate genes was identified as a mediator in the mechanistic pathway of developmental BPA exposure and female-specific energy expenditure, body weight, and body fat phenotypes. Data generated from this study are crucial for deciphering the mechanistic role of epigenetics in the pathogenesis of chronic disease and the development of epigenetic-based prevention and therapeutic strategies for complex human disease.
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Details
- Title
- Novel Epigenetic Biomarkers Mediating Bisphenol A Exposure and Metabolic Phenotypes in Female Mice
- Creators
- Olivia S Anderson - Department of Environmental Health Sciences,Jung H Kim - Department of Environmental Health Sciences.Karen E Peterson - Department of Nutritional Sciences.Brisa N Sanchez - Department of Biostatistics, and.Karilyn E Sant - Department of Environmental Health Sciences.Maureen A Sartor - University of MichiganCaren Weinhouse - Department of Environmental Health Sciences.Dana C Dolinoy - Department of Nutritional Sciences
- Publication Details
- Endocrinology (Philadelphia), v 158(1), pp 31-40
- Grant note
- P30 DK020572 / NIDDK NIH HHS P20 ES018171 / NIEHS NIH HHS P01 ES022844 / NIEHS NIH HHS R01 ES017524 / NIEHS NIH HHS P30 ES017885 / NIEHS NIH HHS P30 DK089503 / NIDDK NIH HHS T32 ES007062 / NIEHS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000397071400004
- Scopus ID
- 2-s2.0-85008429775
- Other Identifier
- 991020099975804721
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- Web of Science research areas
- Endocrinology & Metabolism