| The Mouse Uterotrophic Assay: A Reevaluation of its Validity in Assessing the Estrogenicity of Bisphenol A Caroline M. Markey, Cheryl L. Michaelson, Electra C. Veson, Carlos Sonnenschein, and Ana M. Soto Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts, USA Abstract
The prevalence of synthetic chemicals in our environment that are capable of mimicking the female hormone estrogen is a growing concern. One such chemical, bisphenol A (BPA) , has been shown to leach from a variety of resin-based and plastic products, including dental sealants and food and beverage containers, in concentrations that are sufficient to induce cell proliferation 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 CD-1 mice, a strain that is useful for developmental studies ; and b) whether the uterotrophic assay is a valid means of determining the estrogenicity of BPA by comparing it with other end points measured in the uterus. Immature female CD-1 mice were exposed to BPA in concentrations ranging from 0.1 to 100 mg/kg body weight for 3 days. Results showed that BPA induced a significant 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 in uterine wet weight) was induced by 100 mg/kg BPA only. Further, the proportion 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 intermediate doses of BPA. These results demonstrate that BPA induces changes in the mouse uterus that differ depending on the exposure dose and the end point measured, and reveal that certain tissue effects show a nonmonotonic relationship with dose. These data also demonstrate that BPA induces estrogenic changes in the uterus of the CD-1 mouse, and highlight the need to reevaluate the validity of the mouse uterotrophic assay as an end point for determining the estrogenicity of suspected environmental estrogens. Key words: bisphenol A, CD-1 mouse, endocrine disruptors, lactoferrin, morphometrics, nonmonotonic dose-response curves, uterotrophic assay. Environ Health Perspect 109:55-60 (2001) . [Online 12 December 2000] http://ehpnet1.niehs.nih.gov/docs/2001/109p55-60markey/ abstract.html Address correspondence to A. Soto, Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts 02111-1800 USA. Telephone: (617) 636-6954. Fax: (617) 636-6536. E-mail: asoto@infonet.tufts.edu We thank P. Kwan for technical advice on immunohistochemistry and D. Damassa for invaluable advice on the statistical analysis of data. This work was supported by NIH-ES grant 08314 Received 2 May 2000 ; accepted 19 September 2000.
The full version of this article is available for free in HTML or PDF formats. |
