title: Inducing malignant transformation of endometriosis in rats by long-term sustaining hyperestrogenemia and type II diabetes.
abstract: This study aimed to induce malignant transformation of endometriosis in Sprague-Dawley rats by hyperestrogenemia and type II diabetes and evaluate its similarity with human disease in biological features. Rats with surgically induced endometriosis were randomized into two groups: those treated with estradiol (5 mg/kg three times/week after surgery), streptozotocin (25 mg/kg, 1 month after surgery), and high carbohydrate-and-fat feed (Es group); and those treated with placebo saline and standard feed (control group). All rats were randomly killed 2, 4, or 8 months after surgery. The endometriosis lesions and the corresponding eutopic endometria were subjected to morphological evaluation, TUNEL, and immunohistochemical analysis for the expressions of proliferating cell nuclear antigen, phosphatase and tensin homolog, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin proteins. In the Es group, three cases (6.0%) of endometriosis showed atypical hyperplasia accompanied by simple hyperplastic eutopic endometria, and two cases (4.0%) of endometriosis showed endometrioid carcinoma accompanied by atypical hyperplastic eutopic endometria. In the Es group, the activity of organelles and the expressions of proliferating cell nuclear antigen, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin increased, and the level of phosphatase and tensin homolog and TUNEL positivity decreased progressively in the order of endometriosis, atypical endometriosis, and malignant endometriosis. The same tendency was found in the corresponding eutopic endometria. The induced malignant endometriosis showed similarities with human disease in the pathological process and histomorphological and molecular biological features. The method is feasible. The malignant transformations of endometriosis and eutopic endometria may have correlations and similarities, but the former may suffer a higher risk of canceration.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Chang-Ting
authors.initials: CT
authors.lastname: Wang
authors.forename: Dan-Bo
authors.initials: DB
authors.lastname: Wang
authors.forename: Kui-Ran
authors.initials: KR
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Chun-Xiao
authors.initials: CX
authors.lastname: Sun
authors.forename: Cui-Shan
authors.initials: CS
authors.lastname: Guo
authors.forename: Fang
authors.initials: F
authors.lastname: Ren
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology*; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D016889:Endometrial Neoplasms / Q000209:etiology*; D004715:Endometriosis / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D004967:Estrogens / Q000097:blood* / Q000502:physiology; D005260:Female; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D004967:Estrogens; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat
keywords: Endometrioid adenocarcinoma; endometriosis; hyperestrogenemia; malignant transformation; type II diabetes