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 in trauterine development, is a risk factor for the development of breast canc er. 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 (OPA), on deve lopment of the mammary gland. CD-1 mice were exposed in utero to low, presu mably environmentally relevant doses of BPA (25 and 250 mug/kg body weight) , and their mammary glands were assessed at 10 days, 1 mo, and 6 mo of age. Mammary glands of OPA-exposed mice showed differences in the rate of ducta l migration into the stroma at 1 mo of age and a significant increase in th e percentage of ducts, terminal ducts, terminal end buds, and alveolar buds at 6 mo of age. The percentage of cells that incorporated BrdU was signifi cantly decreased within the epithelium at 10 days of age and increased with in the stroma at 6 mo of age. These changes in histoarchitecture, coupled w ith an increased presence of secretory product within alveoli, resemble tho se of early pregnancy, and they suggest a disruption of the hypothalamic-pi tuitary-ovarian axis and/or misexpression of developmental genes. The alter ed relationship in DNA synthesis between the epithelium and stroma and the increase in terminal ducts and terminal end buds are striking, because thes e changes are associated with carcinogenesis in both rodents and humans.