Professor Caroline Gargett, Professor Luk Rombauts, Professor Grant Montgomery, Dr Caitlin Filby, Dr Brett McKinnon and Dr Sally Mortlock.

To develop a much-needed cure for endometriosis, it is first necessary to understand the pathogenesis and evolution of the disease. Only stem/progenitor cells are sufficiently long-lived and capable to establish endometriotic growths in the pelvis. Our studies have identified and characterised rare populations of two stem/progenitor cell types of the uterine lining. Importantly we have shown that these cells are shed into the pelvic cavity by retrograde menstruation in women with endometriosis, and sometimes in women without the disease.

Endometriosis is a complex disease where many genetic variations confer small effects in combination and through interaction with environmental factors or are involved with the regulation of gene expression. Our studies identified genetic variants for endometriosis risk, but their biological role remains unknown.

Our project is assessing the biological role of these risk variants in endometriosis patients and normal women with few risk variants using gene sequencing and new ways to culture human endometrial cells in 3D organoids, which reflects their function in the body. We are also examining endometrial tissues and lesions to determine the relationships between the risk gene variants, key gene signature genes and stem/progenitor cell locations to further understand the cause of endometriosis and its pathogenesis. We expect our research will increase our understanding on the cause of endometriosis at the genetic, molecular and cellular level, the number two research priority (behind “a cure”) formally identified in the UK. The knowledge generated has translational potential through the identification of genetic and cellular targets for designing new treatments and a diagnostic test based on gene variants.