| The Immature Mouse Is a Suitable Model for Detection of Estrogenicity in the Uterotropic Bioassay Elizabeth Padilla-Banks, Wendy N. Jefferson, and Retha R. Newbold Developmental Endocrinology Section, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Abstract
The traditional rodent uterotropic response assay has been incorporated into the U.S. Environmental Protection Agency's screening and testing program for environmental endocrine-disrupting chemicals (EDCs) . While much effort continues to focus on determining protocol variables, few studies compare uterotropic responses in rats, a species commonly used in toxicologic testing, with other rodent species. In this study, we compared uterine responses in immature outbred CD-1 mice and Sprague-Dawley rats. After three daily subcutaneous injections with 17ß-estradiol (0.1-500 µg/kg/day) , immature mice and rats demonstrated a similar dose-response increase in absolute uterine wet weight and uterine weight:body weight ratio. Further, morphologic and biochemical parameters of estrogenicity, including uterine epithelial cell height and number, gland number, and induction of estrogen-responsive proteins lactoferrin and complement C3, mirror wet weight increases. We conclude that mice are as well suited as rats for the uterotropic bioassay. Because of the advantages of using mice, including lower costs, less space required, and smaller amounts of compound needed for tests, mice should be given appropriate consideration in testing paradigms for EDCs. Key words: complement C3, dose-response modeling, endocrine disruptors, endocrine modulators, environmental estrogens, estrogens, lactoferrin, risk assessment extrapolations, uterotropic bioassay. Environ Health Perspect 109:821-826 (2001) . [Online 13 August] http://ehpnet1.niehs.nih.gov/docs/2001/109p821-826banks/ abstract.html Address correspondence to R.R. Newbold, NIEHS, MD E4-02, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-0738. Fax: (919) 541-4634. E-mail: newbold1@niehs.nih.gov We thank M. Harris for assistance with the rat studies. We also thank M. Sanders and C. Trempus for critical review of the manuscript and W. Stokes, Associate Director for Animal and Alternative Research, NIEHS, for his helpful comments. Received 19 December 2000 ; accepted 20 February 2001.
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