SOTO, A M *; MARKEY, C M; SONNENSCHEIN, C: In utero exposure to bisphenol A alters development of the female genital tract and mammary gland
Exposure to endocrine disruptors is suspected to be the cause of developmental, reproductive and endocrine perturbations found in wildlife, and increases in genital tract malformations, testicular and breast cancer found in humans. Our work focuses on the estrogenic monomer bisphenol A (BPA), which has been shown to leach from dental materials, babies� formula bottles, and food and beverage containers. To test our hypothesis that fetal exposure to BPA induces developmental and reproductive abnormalities, we implanted pregnant CD-1 mice with pumps designed to deliver DMSO (vehicle), 25 and 250 µg/kg BPA from gestational day 9 to 20. These doses are 1/4000 and 1/400 of those required to increase uterine wet weight in prepubescent CD-1 mice. BPA-exposed female offspring showed irregular estrous cycles and significant morphological alterations of the uterus and ovaries. Their mammary glands exhibited decreased epithelial BrdU incorporation (index of DNA synthesis) at 10 days and differences in the rate of ductal migration into the stroma at 1 month of age. A significant increase in the percentage of ducts, terminal ducts, terminal end buds, and alveolar buds was observed at 6 months of age. These changes in histoarchitecture, and the increased presence of secretory product within alveoli, resemble those of early pregnancy, and suggest a disruption of the hypothalamic-pituitary-ovarian axis and/or misexpression of developmental genes. The altered relationship in DNA synthesis between the epithelium and stroma, and the increase in terminal ducts and terminal end buds, is striking since these changes are associated with carcinogenesis in rodents and humans. This work was funded by NIH-ES grant 08314 and Massachusetts Department of Public Health grant 34080066064.
