Bisphenol-A Alters Fetal Mammary Gland Development in Mice

Ana M. Soto, MD
Department of Anatomy and Cellular Biology, Tufts University Medical School
R01ES008314

New work from the laboratory of NIEHS grantee Ana M. Soto at Tufts University School of Medicine illustrates that female mice exposed to bisphenol-A (BPA) in utero from days eight to eighteen of fetal development experience alterations in mammary gland development.

Pregnant female mice were given an environmentally relevant dose of BPA of 250 nanograms per kilogram body weight per day from gestational days 8 to 18, falling within the range of estimated human exposure. The mammary glands of the female offspring of the exposed mice were evaluated on gestational day 18, a time at which ductal branching and fat pad development are underway. Results show that this dose of BPA sped development of the fat pad and altered collagen localization in the stromal region of the glands. In the mammary epithelium, BPA exposure delayed lumen formation and led to decreases in cell size.

BPA was first synthesized in 1891 and was investigated in the 1930s as a synthetic estrogen. It was found to be less estrogenic than other compounds such as diethylstilbestrol and was therefore not used therapeutically as a synthetic estrogen. Its current uses are as a component in polycarbonate plastic and resins. Polycarbonates are widely used in many consumer products including water and food containers and shatter-resistant baby bottles. Some polymers used in dental applications also contain BPA while epoxy resins containing BPA are popular coatings for the inside of cans used for canning food and beverages. BPA has been known to leach from plastics which are cleaned with harsh detergents or used to contain acidic or high temperature liquids. The chemical is found in most people who live in developed countries.

BPA activates estrogen receptors resulting in similar physiological effects as the body’s own naturally occurring estrogens. Other studies demonstrate that fetal exposure to bisphenol A increased the chances of breast cancer in laboratory rats. Soto’s work expands the knowledge of the effects of BPA and suggests that alterations in mammary glands observed at puberty and in adulthood in perinatally exposed mice originate during fetal development.

Citation: Vandenberg LN, Maffini MV, Wadia PR, Sonnenschein C, Rubin BS, Soto AM. Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland. Endocrinology. 2007 Jan;148(1):116-27.