title: Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Microarrays, RT-PCR, laser capture microdissection, and immunohistochemistry were performed with endometrial tissues.
  
  
  METHODS
  This study was performed at a university hospital laboratory.
  
  
  METHODS
  This study comprised 12 regularly cycling women and 12 PCOS patients.
  
  
  METHODS
  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.
authors.affiliation: Department of Obstetrics andGynecology, Cheil General Hospital and Women's Healthcare Center, Kwangdong University College of Medicine, Seoul, Korea.
authors.forename: Jin Yeong
authors.initials: JY
authors.lastname: Kim
authors.forename: Haengseok
authors.initials: H
authors.lastname: Song
authors.forename: Hyunjoo
authors.initials: H
authors.lastname: Kim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Jin Hyun
authors.initials: JH
authors.lastname: Jun
authors.forename: Sung Ran
authors.initials: SR
authors.lastname: Hong
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Koong
authors.forename: In Sun
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004717:Endometrium / Q000473:pathology*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D020869:Gene Expression Profiling; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008597:Menstrual Cycle; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D014158:Transcription, Genetic
chemical_list: D000728:Androgens; D004967:Estrogens; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D012313:RNA; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone