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Combined transcriptomic analyses of endometriosis establishment in the baboon to identify molecular signatures of peritoneal disease for early diagnostic screening

College of Human Medicine, Michigan State University

Principal Investigator(s):

Asgerally T. Fazleabas, PhD

Co-Investigator(s):

Gregory W. Burns, PhD

Institution:

College of Human Medicine, Michigan State University

Abstract:

Endometriosis, a non-malignant disorder defined by the presence of endometrial tissue outside the uterus, is one of the major causes of pelvic pain and impaired fertility. The disease affects 10–15% of reproductive-aged women and retrograde menstruation is thought to be a primary contributor to its etiology. Our current knowledge of the pathogenesis and physiology of ectopic lesion growth, pain, and resultant infertility remains unclear because women have established disease for 8-11 years at the time of clinical diagnosis. Understanding the mechanisms that regulate the development and progression of ectopic lesions at the onset of the disease will result in new opportunities for diagnostics and targeted therapies to prevent and/or treat endometriosis. Earlier diagnosis and treatment would reduce the amount of anatomically distorting scar tissue and pelvic inflammation leading to improved quality of life and fertility in women with endometriosis. The baboon model of induced endometriosis is ideal for understanding the molecular mechanisms involved in the establishment of endometriosis since lesions can be induced that are indistinguishable from human disease and serial sampling is possible. Importantly, the budget- and time-intensive animal experiments are concluded allowing for successful completion of the proposed study. Preliminary data obtained with these samples revealed a distinct microRNA profile of ectopic endometrium indicating that lesions are divergent from their endometrium-derived tissues. Moreover, microRNA networks associated with known disease pathologies, including activation of fibrosis, were identified and provide a molecular framework of pathogenesis. Integrated analyses of altered transcriptomic pathways combined with miRNA expression and key player analysis will identify transcriptomic candidates with robust diagnostic potential and provide meaningful insights into the pathology of the peritoneal disease. These results will improve our understanding of the molecular pathology of peritoneal endometriosis and provide meaningful target molecules for biomarker testing.