Grant: Project Grant

Endometriosis affects 1 in 10 women of reproductive-age. It is defined as tissue from inside the uterus growing in other parts of the body, such as on or near other pelvic organs such as the ovary and colon. Half of women with endometriosis experience sexual pain: specifically deep dyspareunia, defined as pelvic pain with deep penetration during sexual activity. In our recent research, we identified new genetic and molecular pathways by which endometriosis may cause pain with sexual intercourse. Sexual pain in endometriosis is associated with a subtype of endometriosis known as deep infiltrating endometriosis, in which endometriosis invades pelvic organs and forms adhesions. We recently reported the existence of somatic (non-inherited) gene mutations, such as in the KRAS gene, in this type of endometriosis. These mutations may be responsible for the invasive qualities of this type of endometriosis and thus sexual pain. We also have found evidence that sexual pain in endometriosis is associated with increased nerve density around endometriosis. This nerve growth in turn may be under the influence of nerve growth factor and an immune factor known as interleukin-1b (IL-1b). In this proposal, we will validate our findings in a prospective data registry and accompanying tissue bank for endometriosis. Using this large prospective dataset, we will test whether the KRAS (or other gene) mutations are associated with deep infiltrating endometriosis and thus sexual pain. Similarly, we will test whether nerve growth factor and IL-1b are associated with nerve growth around endometriosis and thus sexual pain. We will also develop a new mouse model of endometriosis. In the future we will use this model to test new drugs for endometriosis, which either target the gene mutations, or block nerve growth factor or IL-1b. In 5-10 years of grant end, we propose a clinical trial of the most promising drug, with the aim of providing a new treatment for this common condition.