Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

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.