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Epigenetic Effects of Bisphenol A (BPA): A Literature Review in the Context of Human Dietary Exposure

  • Luísa Camacho
  • Igor P. Pogribny
Reference work entry

Abstract

Bisphenol A (BPA) is a high production volume industrial chemical used widely in the production of polycarbonate plastics and epoxy resins for manufacturing food and drink storage containers, the lining of food cans, dental sealants, medical devices, and thermal paper. Biomonitoring studies show that there is widespread exposure of the human population to BPA, mainly via the diet. The median daily intake of the overall US population is approximately 25 ng BPA/kg body weight (bw)/day, which is estimated to result in serum levels of BPA in the pM range. BPA is an endocrine-disrupting chemical, with known estrogenic activity; more recently, it has been reported to induce epigenetic changes in vitro and in vivo, including effects in DNA methylation, differential histone modifications, and modulation of the levels of noncoding RNAs. This chapter summarizes the studies reporting epigenetic effects associated with human exposure to BPA or induced by the in vitro or in vivo exposure to the chemical. The literature suggesting an association between human exposure to BPA and epigenetic changes is limited. Several studies have assessed the effects of BPA in in vitro cell systems and suggest treatment-related epigenetic effects; the lowest effective BPA dose in vitro was in the nM dose range and the dose-response in these studies tended to be linear. In vivo animal studies suggest epigenetic effects of BPA in a wide range of organs, dose levels, and epigenetic endpoints; however, many studies have limitations, including the use of a single dose level that precludes the characterization of the dose-response of the reported effects. Comprehensive well-designed and well-controlled studies, which include both sexes, multiple and properly spaced BPA doses, multiple time points, and integration of the epigenetic endpoints with other molecular, physiological, and morphological endpoints should provide a better understanding of the potential of BPA to act as an epigenetic modulator.

Keywords

Bisphenol A (BPA) Endocrine-disrupting chemical DNA methylation Histone modification Noncoding RNA microRNA Human In vitro Liver Heart Brain Mammary gland Ovary Uterus Placenta Prostate Testis Sperm 

List of Abbreviations

BPA

Bisphenol A

bw

Body weight

Casq2

Calsequestrin 2

CLARITY-BPA

Consortium Linking Academic and Regulatory Insights on BPA Toxicity

DNMT

DNA methyltransferase

EFSA

European Food Safety Agency

ER

Estrogen receptor

Esrrg

Estrogen-related receptor-γ

Ezh2

Enhancer of zeste 2 polycomb repressive complex 2 subunit

FDA

Food and Drug Administration

Fkbp5

FK506-binding protein 5

GCK

Glucokinase

GD

Gestational day

GPER

G protein-coupled estrogen receptor

H19

Imprinted maternally expressed transcript

Hdac1

Histone deacetylase 1

HOMA

Homeostatic model assessment

HOTAIR

HOX antisense intergenic RNA

HOX

Homeobox

Hpcal1

Hippocalcin-like 1

IAP

Intracisternal A particle

Igf1

Insulin-like growth factor 1

Igf2r

Insulin-like growth factor 2 receptor

LAMP3

Lysosomal-associated membrane protein 3

LINE-1

Long interspersed nuclear elements-1

lncRNA

Long noncoding RNA

miRNA

microRNA

Nsbp1

Nucleosome-binding protein 1

Pde4d4

Phosphodiesterase type 4D variant 4

Peg3

Paternally expressed gene 3

Pgc-1α

Peroxisome proliferator activated receptor-γ, coactivator 1α

PND

Postnatal day

Scgb2a1

Secretaglobin family 2A member 1

SNORD

Small nucleolar RNAs with C/D motif

Sox2

Sex determining region Y box 2

SREBF

Sterol regulatory element-binding transcription factor

StAR

Steroidogenic acute regulatory protein

Stra8

Stimulated by retinoic acid gene 8

Tpd52

Tumor protein D52

β–Cas

β-casein

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© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Division of Biochemical ToxicologyNational Center for Toxicological Research, Food and Drug AdministrationJeffersonUSA

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