The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice

Ayelet Ziv-Gal, Wei Wang, Changqing Zhou, Jodi A. Flaws

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

In utero bisphenol A (BPA) exposure affects reproductive function in the first generation (F1) of mice; however, not many studies have examined the reproductive effects of BPA exposure on subsequent generations. In this study, pregnant mice (F0) were orally dosed with vehicle, BPA (0.5, 20, and 50. μg/kg/day) or diethylstilbestrol (DES; 0.05. μg/kg/day) daily from gestation day 11 until birth. F1 females were used to generate the F2 generation, and F2 females were used to generate the F3 generation. Breeding studies at the ages of 3, 6, and 9. months were conducted to evaluate reproductive capacity over time. Further, studies were conducted to evaluate pubertal onset, litter size, and percentage of dead pups; and to calculate pregnancy rate, and mating, fertility, and gestational indices. The results indicate that BPA exposure (0.5 and 50. μg/kg/day) significantly delayed the age at vaginal opening in the F3 generation compared to vehicle control. Both DES (0.05. μg/kg/day) and BPA (50. μg/kg/day) significantly delayed the age at first estrus in the F3 generation compared to vehicle control. BPA exposure reduced gestational index in the F1 and F2 generations compared to control. Further, BPA exposure (0.5. μg/kg/day) compromised the fertility index in the F3 generation compared to control. Finally, in utero BPA exposure reduced the ability of female mice to maintain pregnancies as they aged. Collectively, these data suggest that BPA exposure affects reproductive function in female mice and that some effects may be transgenerational in nature.

Original languageEnglish (US)
Pages (from-to)354-362
Number of pages9
JournalToxicology and Applied Pharmacology
Volume284
Issue number3
DOIs
StatePublished - May 1 2015
Externally publishedYes

Keywords

  • Bisphenol A (BPA)
  • Diethylstilbestrol (DES)
  • Fertility
  • In utero exposure
  • Transgenerational

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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