Estrogens in the wrong place at the wrong time: Fetal BPA exposure and mammary cancer

Reprod Toxicol. 2015 Jul;54:58-65. doi: 10.1016/j.reprotox.2014.09.012. Epub 2014 Sep 30.


Iatrogenic gestational exposure to diethylstilbestrol (DES) induced alterations of the genital tract and predisposed individuals to develop clear cell carcinoma of the vagina as well as breast cancer later in life. Gestational exposure of rodents to a related compound, the xenoestrogen bisphenol-A (BPA) increases the propensity to develop mammary cancer during adulthood, long after cessation of exposure. Exposure to BPA during gestation induces morphological alterations in both the stroma and the epithelium of the fetal mammary gland at 18 days of age. We postulate that the primary target of BPA is the fetal stroma, the only mammary tissue expressing estrogen receptors during fetal life. BPA would then alter the reciprocal stroma-epithelial interactions that mediate mammogenesis. In addition to this direct effect on the mammary gland, BPA is postulated to affect the hypothalamus and thus in turn affect the regulation of mammotropic hormones at puberty and beyond.

Keywords: Endocrine disruptors; Environmental exposure; Fetal mammary gland; Mammary gland development; Prenatal exposure; Xenoestrogens.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Benzhydryl Compounds / toxicity*
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Communication / drug effects
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Dose-Response Relationship, Drug
  • Endocrine Disruptors / toxicity*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Estrogens / toxicity*
  • Female
  • Gestational Age
  • Humans
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mammary Glands, Human / drug effects*
  • Mammary Glands, Human / growth & development
  • Mammary Glands, Human / metabolism
  • Mammary Glands, Human / pathology
  • Maternal Exposure / adverse effects*
  • Phenols / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Risk Assessment
  • Risk Factors
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Stromal Cells / pathology


  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Estrogens
  • Phenols
  • bisphenol A