Bisphenol-A exposure in utero programs a sexually dimorphic estrogenic state of hepatic metabolic gene expression

Reprod Toxicol. 2017 Aug;71:84-94. doi: 10.1016/j.reprotox.2017.05.001. Epub 2017 May 2.

Abstract

Bisphenol-A (BPA) exposure in utero affects fetal development and metabolism leading to obesity. However, the mechanisms are not well characterized. We identified sexually dimorphic developmental programming of genes regulating metabolism in the liver after BPA exposure. Pregnant mice were treated with BPA on days 9-18 of gestation. At six weeks, female offspring were ovariectomized; both sexes were subsequently treated with estradiol (E2). Fetal BPA exposure altered the expression of genes in liver, including those involved in glucose and lipid metabolism, and transporters, in both sexes. Adult gene expression in BPA-exposed mice often resembled normal adult response to E2 stimulation, even in the absence of estrogen treatment. Estrogen receptor alpha and beta gene expression was upregulated in females and downregulated in males. This is the first report demonstrating sexual dimorphism in liver after BPA exposure and our finding of estrogenization may explain the BPA-related increase in incidence of metabolic disorders and obesity.

Keywords: Bisphenol-A; Gene expression; Liver; Mice; Sexual dimorphism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzhydryl Compounds / blood
  • Benzhydryl Compounds / toxicity*
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor beta / genetics
  • Estrogens / blood
  • Estrogens / pharmacology
  • Estrogens / toxicity*
  • Female
  • Gene Expression Regulation / drug effects*
  • Glucose / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Maternal-Fetal Exchange
  • Mice
  • Phenols / blood
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / metabolism
  • Sex Characteristics

Substances

  • Benzhydryl Compounds
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Phenols
  • Estradiol
  • Glucose
  • bisphenol A