The effects of in utero bisphenol A exposure on ovarian follicle numbers and steroidogenesis in the F1 and F2 generations of mice

Reprod Toxicol. 2017 Dec:74:150-157. doi: 10.1016/j.reprotox.2017.09.013. Epub 2017 Sep 29.


Bisphenol A (BPA) is a commonly used plasticizer. Previous studies show that in utero exposure to BPA affects reproductive outcomes in the F1-F3 generations of mice. However, its multigenerational effects on ovarian histology and steroidogenesis over the reproductive lifespan are unknown. Thus, we tested the hypothesis that BPA has multigenerational effects on follicle numbers and steroidogenesis. Mice were exposed in utero to vehicle control or BPA (0.5, 20, and 50μg/kg/day). Ovaries were collected for histological and gene expression analyses and sera were collected for hormone assays. In utero BPA exposure decreased preantral follicle numbers, cytochrome P450 aromatase mRNA levels, and estradiol levels in the F1 generation, whereas it decreased testosterone levels and altered steroidogenic acute regulatory protein, cytochrome P450 cholesterol side-chain cleavage, 3β-hydroxysteroid dehydrogenase 1, and cytochrome P450 aromatase mRNA levels in the F2 generation. These data suggest that BPA has multigenerational effects on the ovary in mice.

Keywords: Bisphenol A (BPA); Diethylstilbestrol (DES); In utero exposure; Multigenerational; Ovary; Sex steroid hormones; Steroidogenesis.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics
  • Animals
  • Aromatase / genetics
  • Benzhydryl Compounds / toxicity*
  • Cholesterol Side-Chain Cleavage Enzyme / genetics
  • Endocrine Disruptors / toxicity*
  • Estradiol / blood
  • Female
  • Male
  • Maternal-Fetal Exchange
  • Mice
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / metabolism
  • Ovarian Follicle / pathology
  • Phenols / toxicity*
  • Phosphoproteins / genetics
  • Plasticizers / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • RNA, Messenger / metabolism
  • Testosterone / blood


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • Phosphoproteins
  • Plasticizers
  • RNA, Messenger
  • steroidogenic acute regulatory protein
  • Testosterone
  • Estradiol
  • 17-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase
  • Aromatase
  • Cholesterol Side-Chain Cleavage Enzyme
  • bisphenol A