The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay.
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 17beta-estradiol (0.1-500 microg/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.
Padilla-Banks
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Developmental Endocrinology Section, Laboratory of Toxicology, Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Jefferson
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Newbold
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D000818:Animals; D001681:Biological Assay / Q000592:standards*; D001835:Body Weight; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004702:Endocrine Glands / Q000187:drug effects; D004784:Environmental Monitoring / Q000592:standards*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000633:toxicity*; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013045:Species Specificity; D018675:Toxicity Tests / Q000379:methods; D014599:Uterus / Q000473:pathology*
D004958:Estradiol