PILOT PROJECT Endometriosis is one of the most common gynecologic disorders, affecting 10-15% of all reproductive age women, and specifically in 50-60% of women with chronic pelvic pain and infertility. Women with endometriosis have lower conception rates spontaneously or with assisted reproductive technologies. The cost of endometriosis to the U.S. healthcare system was $22 billion in 2002. Current options for women with endometriosis are limited to temporizing symptoms with either medical or surgical treatments. Retrograde menstruation was hypothesized as the primary cause. Molecular studies suggested that altered expression of regulatory genes in the eutopic endometrial tissue promotes implantation and growth of the ectopic endometrial cells. However, little is known about the changes in cellular function in the cellular components of the endometrium leading to the manifestation of endometriosis. Additionally, aberrant molecular pathways associated with endometriosis remain to be defined. Thus, there is a current gap of knowledge at both the cellular and molecular levels impeding the advancement of endometriosis research. Our long term goal is to identify the molecular pathways that promote endometriosis within each functional endometrial cell lineage and apply this knowledge to the development of novel and effective treatments for patients. Our current objective is to define the changes in cellular function in the individual endometrial cell lineage within the endometrium that promote endometriosis and to identify the lineage specific aberrant molecular pathways associated with this disease.
Our aims are 1) to define the changes in cellular function of individual endometrial cell lineage that contribute to the pathogenesis of endometriosis using a mouse transplantation model that allows transplantation of mixtures of singly dissociated endometrial cells and 2) to identify and validate lineage-specific aberrant molecular pathways associated with endometriosis using paired mRNA/mlRNA profiles of highly purified lineage-specific primary and transplanted endometrial cells.
The results from this proposal will define the aberrant molecular pathways and their mediated functional changes most relevant to the manifestation of endometriosis. This will provide a foundation for future studies on the impact of fertility and into the development of targeted therapies for disease-associated infertility and poor pregnancy outcomes in women with endometriosis - a major benefit for the public health.
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