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Gene Expression Analysis of Endometrium Reveals Progesterone Resistance and Candidate Susceptibility Genes in Women with Endometriosis

Department of Obstetrics and Gynecology (R.O.B., M.N., C.R.N.), Stanford University, Stanford, California 94305; Department of Obstetrics, Gynecology, and Reproductive Sciences (S.T., A.E.H., K.C.V., L.C.G.), University of California, San Francisco, San Francisco, California 94143-0138; and Department of Obstetrics and Gynecology (B.A.L.), University Medical Group, Greenville Hospital System, Greenville, South Carolina 29605

Address all correspondence and requests for reprints to: Dr. Linda C. Giudice, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143-0138. E-mail: giudice{at}obgyn.ucsf.edu.

The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

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