Defining the role of RPLP1 in endometriosis and adenomyosis pathophysiology.

Project Summary Adenomyosis and endometriosis are common diseases in women of reproductive age. Both diseases are non-malignant where endometrial gland and stroma tissue grow within the myometrium and pelvic cavity, respectively. Although not as “aggressive” or invasive as endometrial cancers, adenomyosis and endometriosis share several cellular characteristics with malignant endometrial cancer tissue including invasion, migration and augmented cell survival. Further support for underlining similarities among these diseases is the fact and adenomyosis and endometriosis are often comorbid with one another, yet little effort has been made to compare their cellular characteristics side by side. We recently reported that in both endometriosis and adenomyosis (eutopic and ectopic tissues), 60S acidic ribosomal protein P1 (RPLP1) is over-expressed compared to eutopic endometrium from women free of endometriosis/adenomyosis symptomology. RPLP1 upregulation is associated with cellular events conducive to disease pathophysiology including alterations in immune cell population within the endometrium and expression of epithelial-mesenchymal transition (EMT) markers, including RGS1 whose role in EMT is just emerging and has not been examine in the context of uterine diseases. As such, the purpose of this project is to elucidate the role of RPLP1 and RGS1 in regulating the cellular events conducive to endometriosis and adenomyosis pathophysiology. To accomplish this goal we will, 1) define the expression of RPLP1 and RGS1 in adenomyosis and endometriosis tissues and delineate their role in EMT and macrophage differentiation in vitro, and 2) demonstrate the functional role of RPLP1 and RGS1 in mediating disease progression in adenomyosis and endometriosis using in vivo experimental mouse models for both diseases. Together, these experiments will provide insight into novel functions of RPLP1 and RGS1 in mediating common characteristics of both diseases. Outcomes from these studies are anticipated to contribute to the development of less invasive diagnostic markers for adenomyosis and endometriosis as well as identifying potential novel, non-hormonal targets for their treatment.