Grant: Operating Grant

Endometriosis is a major cause of pelvic pain, menstrual disorders and infertility in women. The disease is mainly diagnosed in the peritoneal cavity (abdomen) by the presence of lesions (tumors), which are thought to originate from the endometrium (the inner membrane of the uterus). Endometrial tissue may reach the abdomen during menstruation by circulating in the opposite way, but it is not clear why it implants and grows only in some women. Little is known about the causes of endometriosis and no targeted treatment is available. Our studies were the first to show functional defects in the endometrium, i.e. before this tissue migrates and grows into abnormal locations. Our current main hypothesis is that endometriosis development requires a combination of dysfunctional endometrium and a receptive host tissue. This is supported by our preliminary data showing that in women with endometriosis, the peritoneal host tissue is more responsive to endometrial signals. In fact, we first found high levels of macrophage migration inhibitory factor (MIF), a major growth and inflammatory factor, in the endometrium and initial endometriotic lesions of patients. We then found that MIF stimulates peritoneal cells to release powerful mediator of angiogenesis (development of new blood vessels), inflammation and pain, including prostaglandins (PF; hormones kown to induce labor, pain...), but has much less effect in healthy women. This may facilitate abnormal endometrial tissue growth and contribute to the disease clinical symptoms. Using endometrial, endometriotic and peritoneal tissues, we will first identify what is wrong in PG biosynthesis and use cell culture and co-culture models to investigate how such an abnormal interaction at the endometrial/peritoneal interface plays a role in the development of endometriosis. We will then study the potential benefit of using specific inhibitors of MIF and PG activation pathways to develop specific and more efficient treatment strategies