title: The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice.
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.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: zivgal1@illinois.edu.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Ziv-Gal
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: weiwang2@illinois.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: czhou27@illinois.edu.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: jflaws@illinois.edu.
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D000367:Age Factors; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004971:Estrus / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D005865:Gestational Age; D008098:Litter Size / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D018873:Pregnancy Rate; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012741:Sexual Maturation / Q000187:drug effects; D013997:Time Factors; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A (BPA); Diethylstilbestrol (DES); Fertility; In utero exposure; Transgenerational