Involvement of inflammation in early-stage peritoneal endometriosis

Endometriosis is one of the most frequently encountered benign diseases in gynecology, being the cause of dysmenorrhea, chronic pelvic pain and infertility in more than 35% of women of reproductive age. Decreased quality of life may result not only from symptoms of pelvic pain and infertility, but also from side effects of various medical and surgical treatments. For women with pain, surgery commonly provides temporary relief, but symptoms recur in up to 75% of women within 2 years, and further surgery is needed in many cases.\nThe most widely accepted hypothesis on the origin of peritoneal endometriosis is Sampson’s theory of retrograde menstruation. According to this theory, endometriosis originates from endometrial cells regurgitated through the fallopian tubes, which have the ability to survive, adhere to peritoneum, invade tissues, create a blood supply and proliferate outside their eutopic location. Endometriosis is nowadays considered to be a multifactorial and enigmatic disease. Anatomic, genetic, environmental, hormonal, immunologic and oxidative stress factors have been implicated in the establishment, development, maintenance and progression of endometriotic lesions. \nPeritoneal endometriosis is a chronic pelvic inflammatory disease, characterized by increased numbers of peritoneal macrophages and their secreted products, such as cytokines, growth and angiogenic factors in peritoneal fluid. Inflammation plays a major role in pain and infertility associated with endometriosis, but is also extensively involved in molecular and cellular processes that lead to peritoneal endometriotic lesion development.\nThe aim of this research project was to better characterize endometriosis-associated inflammation and its involvement in early-stage endometriosis development.\nIn the first part of our study, we focused on three inflammatory pathways implicated in the pathogenesis of endometriosis, highlighting the involvement of peritoneal macrophages: peritoneal iron metabolism, NF-κB activation and prostaglandin biosynthesis. According to available data from our studies and the literature, these three pathways may be linked and potential molecular interactions are considered.\nThe second part of our project was designed to evaluate the impact of treating endometrial cells by proinflammatory cytokines on the adhesion process to mesothelial cells. The establishment and validation of an original in vitro experimental model are also described.\nA fundamental understanding of the inflammatory response is essential to better target the development of new therapeutic approaches in endometriosis, as well as in other pathogenic processes involving cellular adhesion and inflammation.