Developmental programming: Changes in mediators of insulin sensitivity in prenatal bisphenol A-treated female sheep

Reprod Toxicol. 2019 Apr;85:110-122. doi: 10.1016/j.reprotox.2019.03.002. Epub 2019 Mar 7.


Developmental exposure to endocrine disruptor bisphenol A (BPA) is associated with metabolic defects during adulthood. In sheep, prenatal BPA treatment causes insulin resistance (IR) and adipocyte hypertrophy in the female offspring. To determine if changes in insulin sensitivity mediators (increase in inflammation, oxidative stress, and lipotoxicity and/or decrease in adiponectin) and the intracrine steroidal milieu contributes to these metabolic perturbations, metabolic tissues collected from 21-month-old female offspring born to mothers treated with 0, 0.05, 0.5, or 5 mg/kg/day of BPA were studied. Findings showed prenatal BPA in non-monotonic manner (1) increased oxidative stress; (2) induced lipotoxicity in liver and muscle; and (3) increased aromatase and estrogen receptor expression in visceral adipose tissues. These changes are generally associated with the development of peripheral and tissue level IR and may explain the IR status and adipocyte hypertrophy observed in prenatal BPA-treated female sheep.

Keywords: Bisphenol A; Endocrine disruptor; Inflammation; Insulin resistance; Lipotoxicity; Oxidative stress.

Publication types

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

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Benzhydryl Compounds / toxicity*
  • Dyslipidemias / chemically induced
  • Endocrine Disruptors / toxicity*
  • Female
  • Fetal Development
  • Insulin Resistance*
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Maternal-Fetal Exchange
  • Muscles / drug effects
  • Muscles / metabolism
  • Oxidative Stress / drug effects
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Sheep


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • bisphenol A