Induction of decidualization of endometrial stromal cells as a therapeutical approach for the treatment of endometriosis

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Endometriosis is characterized by the presence of endometrial tissue in ectopic locations and leads to severe abdominal pain and subfertility. Moreover, current medical treatment is associated with undesirable side effects and high recurrence rates. Since endometrial stromal cells play a pivotal role in the establishment of this disease, and terminal differentiation (decidualization) of these cells has been shown to be impaired in endometriosis patients, induction of decidualization of ectopic endometrial stromal cells may be a promising target for innovative therapeutical approaches. Thus the aim of the project is to discover potential inductors of decidualization and apoptosis of endometrial stromal cells of endometriosis patients. Based on the finding that the progesterone receptor pathway as well as cAMP-mediated signalling is involved in induction of decidualization, compounds interacting with these pathways will be analyzed in regard to their potential to induce differentiation of endometrial stromal cells from women with and without endometriosis. Effective compounds and compound combinations will be evaluated in vitro using primary culture of endometrial stromal cells of both study groups. Thereafter, the most promising agents will be evaluated in an endometriosis mouse model in regard to their potential to induce decidualization of ectopic endometrial lesions in vivo. The respective effect on decidualization will be evaluated by morphologic parameters and by quantification of the decidualization marker prolactin. Moreover, the effect of these compounds on proliferation, apoptosis, and angiogenesis will be analyzed. The potency of the compounds tested on induction of decidualization and regression of lesions will be correlated to the receptor status of the endometrium of single patients, targeting on the development of individualized therapeutical approaches.