A seed or soil problem in early endometriosis: stromal cell origin drives cellular invasion and coupling over mesothelial cell origin

Abstract

To study the role of the mesothelial cells in early endometriosis lesion formation by assessing in vitro cell to cell communication and invasion of endometrial cells across a mesothelial cell monolayer, with both cell types derived from both endometriosis and control patients. Laboratory based experimental study SETTING: University hospital and laboratory PATIENT(S): Consenting reproductive aged women who underwent laparoscopy for gynecologic reasons and were confirmed to either have endometriosis with pathology tissue diagnosis (n=8) or no endometriosis (n=8) at the time of surgery INTERVENTION: Primary stromal cells cultured from endometrial pipelle biopsies and primary mesothelial cells cultured from peritoneal explants were utilized in trans-mesothelial invasion assays and gap junction coupling assays. Comparison of potential for lesion formation, using in vitro models, of both primary endometrial and mesothelial cells from endometriosis and control patients, establishing the former as the primary disease driver. When comparing mesothelial cells from control patients to mesothelial cells from endometriosis patients, there was no significant difference in the amount of stromal cell invasion across either barrier. In contrast, when comparing stromal cell origin, the amount of invasion by endometriosis stromal cells was greater than control stromal cells regardless of whether the mesothelial cell monolayer was derived from disease or control patients. Additionally, primary mesothelial cells induced more gap junction coupling, a requirement for invasion, in stromal cells from endometriosis than control patients, again independent of mesothelial origin. The notable exception was mesothelial cells derived from endometriotic lesion affected areas that showed depressed ability to support invasion. While both endometrial and mesothelial cells need to function for establishment of endometriosis lesions, the endometrium seems to be the key player, serving as an ideal target for diagnostic strategies and therapeutic intervention. This notion is consistent with prior studies, however we are the first to directly test both primary mesothelial and endometrial cells from endometriosis and control patients to compare propensities for mesothelial invasion.