Establishment of a novel model of endometriosis-associated ovarian cancer by transplanting uterine tissue from Arid1a/Pten knockout mice

Abstract

Although endometriosis is primarily benign, it has been identified as a risk factor for endometriosis-associated ovarian cancer (EAOC). Genetic alterations in ARID1A, PTEN, and PIK3CA have been reported in EAOC; however, an appropriate EAOC animal model has yet to be established. Therefore, the present study aimed to create an EAOC mouse model by transplanting uterine pieces from donor mice, in which Arid1a and/or Pten was conditionally knocked out (KO) in Pax8-expressing endometrial cells by the administration of doxycycline (DOX), onto the ovarian surface or peritoneum of recipient mice. Two weeks after transplantation, gene KO was induced by DOX and endometriotic lesions were thereafter removed. The induction of only Arid1a KO did not cause any histological changes in the endometriotic cysts of recipients. In contrast, the induction of only Pten KO evoked a stratified architecture and nuclear atypia in the epithelial lining of all endometriotic cysts, histologically corresponding to atypical endometriosis. The induction of Arid1a; Pten double-KO evoked papillary and cribriform structures with nuclear atypia in the lining of 42 and 50% of peritoneal and ovarian endometriotic cysts, respectively, which were histologically similar to EAOC. These results indicate that this mouse model is useful for investigating the mechanisms underlying the development of EAOC and the related microenvironment.

Endometriosis-Associated Ovarian Cancer: From Molecular Pathologies to Clinical Relevance

“…To identify new therapeutic targets interfering with the underlying molecular pathology, several animal models were developed, including mice with a conditional doxycyclineinduced Arid1a and/or Pten knockout [178], mice with endometrial autoimplantation and 7,12-Dimethylbenz[a]anthracene (DMBA) tumor induction [179].…”

Research progress in endometriosis-associated ovarian cancer

“…Recently, based on the establishment of animal models of endometriosis, successful reports of establishing EAOC mouse models have also emerged ( 93 ). By simulating tumor characteristics and reproducing the biological properties of tumors, these models can provide important reference for clinical precision treatment research, which is crucial for the study and development of precision treatment for EAOC.…”