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Transcriptional Profiling with a Pathway-Oriented Analysis Identifies Dysregulated Molecular Phenotypes in the Endometrium of Patients with Polycystic Ovary Syndrome

Laboratory of Reproductive Biology and Infertility (H.S., H.K., H.J.K., J.H.J.) and Departments of Obstetrics and Gynecology (J.Y.K., M.K.K.) and Pathology (S.R.H), Cheil General Hospital and Women’s Healthcare Center, Kwangdong University College of Medicine, Seoul, Korea 100-380; and Department of Pathology (J.Y.K., I.S.K.), Korea University College of Medicine, Seoul, Korea 136-701

Address all correspondence and requests for reprints to: Haengseok Song, Ph.D., Laboratory of Reproductive Biology and Infertility, Cheil General Hospital, Kwandong University College of Medicine, 1-19, Mukjeong-dong, Jung-gu, Seoul 100-380, Korea. E-mail: haengseok{at}gmail.com; or In Sun Kim, M.D., Department of Pathology, Korea University College of Medicine. E-mail: iskim{at}korea.ac.kr.

Context: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligo/anovulation, hyperandrogenemia, infertility, and metabolic alterations related to insulin resistance. These abnormalities in PCOS may have complex effects on pathophysiology of the endometrium, contributing to infertility and endometrial disorders.

Objective: The objective of this study was to examine dysregulated signaling pathways in the endometrium of patients with PCOS (PCOSE) by analyzing expression profiles with a pathway-oriented method.

Design: Microarrays, RT-PCR, laser capture microdissection, and immunohistochemistry were performed with endometrial tissues.

Setting: This study was performed at a university hospital laboratory.

Patients: This study comprised 12 regularly cycling women and 12 PCOS patients.

Main Outcome Measure: Dysregulated signaling pathways in PCOSE were identified as a gene set.

Results: Hierarchical clustering revealed distinct expression profiles for PCOSE and the endometrium of normal cycling women. Gene sets associated with androgen signaling were not enriched in PCOSE, although they affect ovarian physiology of PCOS patients. Several biological pathways including cell cycle, apoptosis, glycolysis, and integrin-Rho-cytoskeleton network were aberrantly down-regulated in PCOSE. Expression of genes constituting these gene sets enriched in normal cycling women was systemically down-regulated in PCOSE. Laser capture microdissection-coupled real-time RT-PCR and immunohistochemistry further demonstrated that cell proliferation in the stroma, but not the epithelium, is significantly reduced in PCOSE.

Conclusions: Systemic down-regulation of various signaling pathways in PCOSE with extremely prolonged proliferative phase provides insight into the abnormal phenotypes that reflect pathophysiology of PCOS in the endometrium, possibly leading to increased risks of endometrial disorders.

This article has been cited by other articles:

				R. S. Legro and J. M. McAllister Heirarchical Clustering and Beyond in PCOS Endometrium: Brave New World J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1084 - 1085. [Full Text] [PDF]