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Transcriptional Characterizations of Differences between Eutopic and Ectopic Endometrium

Deparments of Pediatrics (Y.W., P.J., X.W., S.G., S.-W.G.), Obstetrics and Gynecology (E.S., G.H.), and Pathology (Z.B.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226; Department of Pathology (A.K.-B.), University of Illinois, Chicago, Illinois 60612; and Department of Statistics and Applied Probability (Y.W.), University of California, Santa Barbara, California 93106

Address all correspondence and requests for reprints to: Sun-Wei Guo, Ph.D., Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, MS 756, Milwaukee, Wisconsin 53226-0509. E-mail: swguo{at}mcw.edu.

Endometriosis, defined as the presence of endometrial glandular and stromal cells outside the uterine cavity, is a common gynecological disease with poorly understood pathogenesis. Using laser capture microdissection and a cDNA microarray with 9600 genes/expressed sequence tags (ESTs), we have conducted a comprehensive profiling of gene expression differences between the ectopic and eutopic endometrium taken from 12 women with endometriosis adjusted for menstrual phase and the location of the lesions. With dye-swapping and replicated arrays, we found 904 genes/ESTs that are differentially expressed. We validated the gene expression using real-time RT-PCR. We found that the expression patterns of these genes/ESTs correctly classified the 12 patients into ovarian and nonovarian endometriosis. We identified gene clusters that are location-specific. In addition, we identified several biological themes using Expression Analysis Systematic Explorer. Finally, we identified 79 pathways with over 100 genes with known functions, which include oxidative stress, focal adhesion, Wnt signaling, and MAPK signaling. The identification of these genes and their associated pathways provides new insight. Our findings will stimulate future investigations on molecular genetic mechanisms underlying the pathogenesis of endometriosis.

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