The mouse uterotrophic assay: A reevaluation of its validity in assessing the estrogenicity of bisphenol A

The prevalence of synthetic chemicals in our environment that are capable o f mimicking the female hormone estrogen is a growing concern. One such chem ical, bisphenol A (BPA), has been shown to leach from a variety of resin-ba sed and plastic products, including dental sealants and food and beverage c ontainers, in concentrations that are sufficient to induce cell proliferati on in vitro. The response to BPA in vivo has been varied; thus the aims of this study were to investigate a) whether BPA has an estrogenic effect in C D-1 mice, a strain that is useful for developmental studies; and b) whether the uterotrophic assay is a valid means of determining the estrogenicity o f BPA by comparing it with other end points measured in the uterus. Immatur e female CD-1 mice were exposed to BPA in concentrations ranging from 0.1 t o 100 mg/kg body weight for 3 days. Results showed that BPA induced a signi ficant increase in the height of luminal epithelial cells within the uterus at concentrations of 5, 75, and 100 mg/kg and that BPA induced lactoferrin at concentrations of 75 and 100 mg/kg. A uterotrophic response (increase i n uterine wet weight) was induced by 100 mg/kg BPA only. Further, the propo rtion of mice showing vaginal opening was greater after exposure to 0.1 and 100 mg/kg BPA, relative to the control animals and those receiving interme diate doses of BPA. These results demonstrate that BPA induces changes in t he mouse uterus that differ depending on the exposure dose and the end poin t measured, and reveal that certain tissue effects show a nonmonotonic rela tionship with dose. These data also demonstrate that BPA induces estrogenic changes in the uterus of the CD-1 mouse, and highlight the need to reevalu ate the validity of the mouse uterotrophic assay as an end point for determ ining the estrogenicity of suspected environmental estrogens.