background on bisphenol A

Ramos, JG, J Varayoud, C Sonnenschein, AM Soto, M Muñoz de Toro and EH Luque. 2001. Prenatal Exposure to Low Doses of Bisphenol A Alters the Periductal Stroma and Glandular Cell Function in the Rat Ventral Prostate. Biology of Reproduction 65: 1271–1277.

What did they do?
What did they find?
What does it mean?

Ramos et al. demonstrate that bisphenol A contamination at low levels in the womb causes significant alterations in the development of the rat prostate. Their study is especially valuable because it provides detailed microscopic information about the ways that low-level bisphenol A (BPA) affects prostate structure.

Their results demonstrate that rats exposed to BPA in the womb experience alterations in cell function within the prostate at puberty. Some of the changes resemble conditions in the human prostate that enhance the potential of a nascent prostate cancer tumor. Hence these results point toward the potential involvement of in utero exposure to bisphenol A and other environmental estrogens in prostate cancer.

What did they do? Ramos et al. exposed fetal mice to bisphenol A via osmotic pumps implanted in female rats during pregnancy. BPA was delivered from day 8 of pregnancy through to delivery (day 23) at either 25 µg/kg female body weight (parts per billion) or 250 µg/kg. They then compared the exposed males to a control group with respect to a series of microscopic measurements and immunochemical assays in different tissues within the prostate.

What did they find? The prostates of males exposed in the womb were significantly different from unexposed males by the time of puberty, at both exposure levels used in the experiment. The differences involved changes in structure, changes in the distribution of androgen receptors, and alterations in immunohistochemistry of different tissue types.

red dot indicates a significant difference from control

Expression of the protein vimentin increased in treated animals compared to controls. In untreated animals, cells expressing vimentin form a discontinuous ring in the periductal region of the prostate. In BPA-treated animals, however, the vimentin+ cells formed a "continuous uniform halo around the proximal and distal ducts."

Expression of a-SMA decreased in treated animals. In untreated animals, cells expressing this protein form a continuous ring around the ducts. Following BPA treatment, the ring becomes discontinuous.

The percentage of prostate stromal cells testing positive for androgen receptors decreases following BPA treatment.

The percentage of epithelial cells expressing the enzyme prostate acidic phosphatase (PAP) decreased in BPA treated animals.

What does it mean? These findings show that prenatal exposure to low, environmentally relevant doses of BPA induces abnormalities in the development of the rat prostate, with effects observable after puberty. Tissue organization and protein expression are altered. Fewer androgen-sensitive cells are present. The structural changes involve changes in the differentiation pattern of the periductal stromal cells of the rat ventral prostate: BPA-treated animals develop a thick layer of vimentin-positive and a-SMA-negative cells in the periductal zone.

In humans, alterations in the stroma appear to enhance the invasive and/or malignant potential of a new tumor (Grossfield et al. 1998). The discoveries by Ramos et al. about low-level bisphenol A impacts on stromal cells in the rat ventral prostate should lead to intensified research on the links between BPA and human prostate cancer, and immediate reductions in human exposure to BPA as a precautionary measure.

Industry asserts that decades of experience with BPA demonstrates its safety. Over those decades, many—probably millions—of human fetuses have been exposed to BPA and other environmental estrogens. In the latter half of the 20th century in the US, the incidence of prostate cancer increased significantly. No epidemiological study with the data necessary to carry out a plausible test has ever (as of 1 January 2002) examined the potential link between prostate cancer and environmental estrogen exposure in the womb. Hence industry's claim about the demonstrated safety of BPA is clearly false.