Analysis Tools
reproductive system
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• chronic exposure to low levels of estrogen for 12 weeks increases the severity of epithelial atypia and induces multifocal endometrial adenocarcinoma in mutant, but not in wild-type, females
• in estrogen-treated homozygotes, endometrial glands appear crowded and more complex with cribiform changes that form epithelial nodules, while cells appear large and hypochromatic with numerous mitoses
• however, no invasive carcinoma is observed in untreated mutant or wild-type females at >1 year of age
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• at 3-6 months of age, female homozygotes display a disorganized luminal endometrium with significant epithelial proliferation and cytologic atypia
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• at 3-6 months of age, female homozygotes exhibit tortuous endometrial glands of increased complexity
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• at 3-6 months of age, female homozygotes display a hyperplastic luminal endometrium; the luminal epithelium is overgrown forming epithelial knots that protrude into the lumen
• a severe cytologic anomaly ranging from atypical hyperplasia to carcinoma in situ is observed in the surface and glandular epithelium
• at 1 year of age, atypical and cystic hyperplasia is still evident, although the proliferative component is reduced while cystic changes are enhanced relative to 3-6 months of age
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• mutant uterine tracts are abnormally enlarged
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• mutant uterine tracts are abnormally distended
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• whereas 14 matings between wild-type female and male mice result in 100 pups, 26 matings between homozygous mutant females and males yield only 71 pups, indicating reduced female fertility
• however, the overall length of the estrous cycle remains unaffected
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• homozygous mutant females produce significantly smaller litter sizes relative to wild-type females (2.73 2.71 vs 7.21 3.24 pups/litter, respectively)
• fetal resorption is observed in mutant, but not in wild-type, female mice
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neoplasm
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• chronic exposure to low levels of estrogen for 12 weeks increases the severity of epithelial atypia and induces multifocal endometrial adenocarcinoma in mutant, but not in wild-type, females
• in estrogen-treated homozygotes, endometrial glands appear crowded and more complex with cribiform changes that form epithelial nodules, while cells appear large and hypochromatic with numerous mitoses
• however, no invasive carcinoma is observed in untreated mutant or wild-type females at >1 year of age
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endocrine/exocrine glands
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• at 3-6 months of age, female homozygotes exhibit tortuous endometrial glands of increased complexity
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