Endometriosis Susceptibility Genes in Endometrial Stem/Progenitor Cells

ABSTRACT

To develop a much-needed cure for endometriosis, it is first necessary to understand the pathogenesis and evolution of the disease. Endometrial stem/progenitor cells have been implicated as well as multiple genetic variations, each contributing a small effect but combined may have as yet unknown biological roles. A single polygenic risk score (PRS) can be used to categorize this genetic load of the risk variants in an individual. In this project, we will assess the biological role of a high PRS in endometriosis patients versus a low PRSin normal women. Specifically, we will assess changes in gene expression in endometrial cells of eutoptic endometrium at the single cell level, functional behavior of endometrial stem/progenitor cells in organoid assays, including co-culture with stromal cells and localization of risk gene variants, and key gene signatures in relation to stem/progenitor cell locations. We have completed all required approvals, developed new tools, questionnaire, databases, assays and protocols, recruited 9 women and collected samples for all 3 aims in spite of significant challenges faced with the timing of HRPO approval and COVID-19 impacts on gynecological surgeries. As surgeries recommence following easing of 8 months COVID-19 restrictions in Melbourne, we have participants waiting for their delayed surgeries and we are ready to accelerate progress in Aims 1 and 2 in the second reporting period.