Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis

Objective: To investigate interactions between peritoneal macrophages and endometrial stromal cells (ESCs) involved in the development of endometriosis. Design: Clinicopathologic and in vitro studies. Setting: Department of Obstetrics and Gynecology and Department of Pathology, Kumamoto University Hospital. Patient(s): Women undergoing laparoscopy or laparotomy to treat endometriosis or other benign gynecologic conditions. Intervention(s): We collected samples of peritoneal fluid (ascites), endometrium, and endometriotic tissues. We cocultured ESCs in vitro with or without human macrophages. Main Outcome Measure(s): Macrophage phenotypes in peritoneal fluid were determined via immunostaining. Proliferation of ESCs and activation of signal transducer and activator of transcription-3 (Stat3) in cocultures were evaluated. Result(s): The endometriosis group had a significantly higher total number of macrophages in ascites compared with the control group, but the ratios of D163 vertical bar alternatively activated macrophages (M2) in the two groups did not differ significantly. Coculture with M2 macrophages significantly up-regulated ESC proliferation and Stat3 activation in ESCs in vitro. Proliferation of ESCs was suppressed after Stat3 was down-regulated by small interfering RNA. Stat3 was activated in epithelial cells and ESCs in human endometriotic lesions. Conclusion(s): Interactions between M2 macrophages and ESCs via Stat3 activation may play an important role in the development of endometriosis. ((c) 2013 by American Society for Reproductive Medicine.)