Early Exposure to Bisphenol A Alters Mouse Mammary Gland Development

Ana M. Soto, MD, Ph.D.
Tufts University School of Medicine
R01ES08314

Background: Bisphenol A is a compound found in the plastic liners of beverage and food cans, plastic bottles, and in dental sealants used widely in young children to prevent cavities. It is known to leach from the plastic, especially when in contact with acidic substances. It has estrogen-like properties and in a recent study was found in 95% of human urine samples. Because of the widespread use of the chemical and its proven human exposure, concern for potential reproductive and developmental effects is growing.

Other environmental estrogens have been shown to have effects on the developing mammary gland. To determine whether bisphenol A has similar effects, an NIEHS-supported research team exposed pregnant mice to low doses of the compound and examined the mammary development of their female offspring. The doses used were among the lowest tested in the published literature and are within the range of human exposures.

Advance: Results of the study show that perinatal bisphenol A exposure enhanced the mammary gland’s sensitivity to estradiol later in life. The compound increased the number of terminal end buds, the structures where cancer arises later in life. The study also showed that bisphenol A altered the growth of the mammary gland ducts during puberty and it increased the number of cells expressing the progesterone receptor, and hence, the likelihood of increased sensitivity to progesterone. Lateral branching of the ductal system was significantly enhanced at 4 months of age in the bisphenol A exposed animals presumably due to increased progesterone action. The mammary glands contained significantly more ductal structures than those from the control animals. This is an important finding because in humans, increased mammographic density is an established risk factor for breast cancer.

Implications: The bisphenol A induced increases in terminal end bud density at puberty as well as the increased numbers of ducts reported previously by this laboratory in adult animals are most troubling, since these two structures are the sites where cancer arises in humans and rodents. These findings suggest that bisphenol A exposure in humans may be an important risk factor for breast cancer and should be studied more intensely.

Citation: Munoz-de-Toro M, Markey C, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, Soto AM. Perinatal exposure to Bisphenol A alters peripubertal mammary gland development in mice. Endocrinology. 2005 May 26; [Epub ahead of print]