In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

Wei Wang, Katlyn S. Hafner, Jodi A. Flaws

Research output: Contribution to journalArticlepeer-review

Abstract

Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05. μg/kg, positive control), or BPA (0.5, 20, and 50. μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30. days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalToxicology and Applied Pharmacology
Volume276
Issue number2
DOIs
StatePublished - Apr 15 2014
Externally publishedYes

Keywords

  • Apoptosis
  • Bisphenol A
  • Fertility
  • Follicle
  • Germ cell nest breakdown
  • Ovary

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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