Unbound MEDLINE

Bisphenol A inhibits follicle growth and induces atresia in cultured mouse antral follicles independently of the genomic estrogenic pathway.

Abstract

Bisphenol A (BPA) is an estrogenic chemical used to manufacture many commonly used plastic and epoxy resin-based products. BPA ubiquitously binds to estrogen receptors throughout the body, including estrogen receptor alpha (ESR1) in the ovary. Few studies have investigated the effects of BPA on ovarian antral follicles. Thus, we tested the hypothesis that BPA alters cell cycle regulators and induces atresia in antral follicles via the genomic estrogenic pathway, inhibiting follicle growth. To test this hypothesis, we isolated antral follicles from 32- to 35-day-old control and Esr1-overexpressing mice and cultured them with vehicle control (dimethylsulfoxide [DMSO]) or BPA (1-100 μg/ml). Additionally, antral follicles were isolated from 32- to 35-day-old FVB mice and cultured with DMSO, BPA (1-100 μg/ml), estradiol (10 nM), ICI 182,780 (ICI; 1 μM), BPA plus ICI, or BPA plus estradiol. Follicles were measured for growth every 24 h for 96-120 h and processed either for analysis of estrogen receptor, cell cycle, and/or atresia factor mRNA expression, or for histological evaluation of atresia. Results indicate that estradiol and ICI do not protect follicles from BPA-induced growth inhibition and that estradiol does not protect follicles from BPA-induced atresia. Furthermore, overexpressing Esr1 does not increase susceptibility of follicles to BPA-induced growth inhibition. Additionally, BPA up-regulates Cdk4, Ccne1, and Trp53 expression, whereas it down-regulates Ccnd2 expression. BPA also up-regulates Bax and Bcl2 expression while inducing atresia in antral follicles. These data indicate that BPA abnormally regulates cell cycle and atresia factors, and this may lead to atresia and inhibited follicle growth independently of the genomic estrogenic pathway.

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  • Publisher Full Text

    • Authors

    Peretz J, Craig ZR, Flaws JA

    Institution

    Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

    Source

    Biology of reproduction 87:3 2012 Sep pg 63

    MeSH

    Air Pollutants, Occupational
    Animals
    Benzhydryl Compounds
    Cells, Cultured
    Down-Regulation
    Estrogen Receptor alpha
    Female
    Follicular Atresia
    Gene Expression Regulation
    Genes, cdc
    Genome
    Mice
    Mice, Transgenic
    Ovarian Follicle
    Phenols
    Signal Transduction

    Pub Type(s)

    Evaluation Studies
    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    22743301