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Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model.


ABSTRACT: Endometriosis results from ectopic invasion of endometrial tissue within the peritoneal cavity. Aberrant levels of the estrogen receptor (ER), ER? and ER?, and higher incidence of autoimmune disorders are observed in women with endometriosis. An immunocompetent mouse model of endometriosis was used in which minced uterine tissue from a donor was dispersed into the peritoneal cavity of a recipient. Wild-type (WT), ER?-knockout (?ERKO), and ?ERKO mice were donors or recipients to investigate the roles of ER?, ER?, and estradiol-mediated signaling on endometriosis-like disease. Mice were treated with vehicle or estradiol, and resulting location, number, and size of endometriosis-like lesions were assessed. In comparison with WT lesions in WT hosts, ?ERKO lesions in WT hosts were smaller and fewer in number. The effect of ER status and estradiol treatment on nuclear receptor status, proliferation, organization, and inflammation within lesions were examined. ?ERKO lesions in WT hosts did not form distal to the incision site, respond to estradiol, or proliferate but did have increased inflammation. WT lesions in ?ERKO hosts did respond to estradiol, proliferate, and show decreased inflammation with treatment, but surprisingly, progesterone receptor expression and localization remained unchanged. Only minor differences were observed between WT lesions in ?ERKO hosts and ?ERKO lesions in WT hosts, demonstrating the estradiol-mediated signaling responses are predominately through ER?. In sum, these results suggest ER in both endometriosis-like lesions and their environment influence lesion characteristics, and understanding these interactions may play a critical role in elucidating this enigmatic disease.

SUBMITTER: Burns KA 

PROVIDER: S-EPMC3404357 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model.

Burns Katherine A KA   Rodriguez Karina F KF   Hewitt Sylvia C SC   Janardhan Kyathanahalli S KS   Young Steven L SL   Korach Kenneth S KS  

Endocrinology 20120614 8


Endometriosis results from ectopic invasion of endometrial tissue within the peritoneal cavity. Aberrant levels of the estrogen receptor (ER), ERα and ERβ, and higher incidence of autoimmune disorders are observed in women with endometriosis. An immunocompetent mouse model of endometriosis was used in which minced uterine tissue from a donor was dispersed into the peritoneal cavity of a recipient. Wild-type (WT), ERα-knockout (αERKO), and βERKO mice were donors or recipients to investigate the r  ...[more]

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