In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland

Exposure to estrogens throughout a woman’s life, including the period of intrauterine development, is a risk factor for the development of breast cancer. The increased incidence of breast cancer noted during the last 50 years may have been caused, in part, by exposure of women to estrogen-mimicking chemicals that are released into the environment. Here, we investigated the effects of fetal exposure to one such chemical, bisphenol A (BPA), on development of the mammary gland. CD-1 mice were exposed in utero to low, presumably environmentally relevant doses of BPA (25 and 250 mg/kg body weight), and their mam-mary glands were assessed at 10 days, 1 mo, and 6 mo of age. Mammary glands of BPA-exposed mice showed differences in the rate of ductal migration into the stroma at 1 mo of age and a significant increase in the percentage of ducts, terminal ducts, terminal end buds, and alveolar buds at 6 mo of age. The per-centage of cells that incorporated BrdU was significantly de-creased within the epithelium at 10 days of age and increased within the stroma at 6 mo of age. These changes in histoarchi-tecture, coupled with an increased presence of secretory prod-uct within alveoli, resemble those of early pregnancy, and they suggest a disruption of the hypothalamic-pituitary-ovarian axis and/or misexpression of developmental genes. The altered rela-tionship in DNA synthesis between the epithelium and stroma and the increase in terminal ducts and terminal end buds are striking, because these changes are associated with carcinogen-esis in both rodents and humans. developmental biology, environment, mammary glands, mecha-nisms of hormone action, toxicolog