Bisphenol A inhibits cultured mouse ovarian follicle growth partially via the aryl hydrocarbon receptor signaling pathway

Reprod Toxicol. 2013 Dec:42:58-67. doi: 10.1016/j.reprotox.2013.07.022. Epub 2013 Aug 6.

Abstract

Bisphenol A (BPA) is an endocrine disruptor that inhibits growth of mouse ovarian follicles and disrupts steroidogenesis at a dose of 438μM. However, the effects of lower doses of BPA and its mechanism of action in ovarian follicles are unknown. We hypothesized that low doses of BPA inhibit follicular growth and decrease estradiol levels through the aryl hydrocarbon receptor (AHR) pathway. Antral follicles from wild-type and Ahr knock-out (AhrKO) mice were cultured for 96h. Follicle diameters and estradiol levels then were compared in wild-type and AhrKO follicles ± BPA (0.004-438μM). BPA inhibited follicle growth (110-438μM) and decreased estradiol levels (43.8-438μM) in wild-type and AhrKO follicles. However, at BPA 110μM, inhibition of growth in AhrKO follicles was attenuated compared to wild-type follicles. These data suggest that BPA may inhibit follicle growth partially via the AHR pathway, whereas its effects on estradiol synthesis likely involve other mechanisms.

Keywords: AHR; Antral follicle; BPA; Estradiol; Low dose; Ovary.

Publication types

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

MeSH terms

  • Animals
  • Benzhydryl Compounds / toxicity*
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Environmental Pollutants / toxicity*
  • Estradiol / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / growth & development
  • Ovarian Follicle / metabolism
  • Phenols / toxicity*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction / drug effects
  • bcl-2-Associated X Protein / genetics

Substances

  • Bax protein, mouse
  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Environmental Pollutants
  • Phenols
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Aryl Hydrocarbon
  • bcl-2-Associated X Protein
  • Estradiol
  • bisphenol A