title: Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS), the most common endocrinopathy of reproductive-aged women, is characterized by ovulatory dysfunction and hyperandrogenism.
  
  
  OBJECTIVE
  The aim was to compare gene expression between endometrial samples of normal fertile controls and women with PCOS.
  
  
  METHODS
  We conducted a case control study at university teaching hospitals.
  
  
  METHODS
  Normal fertile controls and women with PCOS participated in the study.
  
  
  METHODS
  Endometrial samples were obtained from normal fertile controls and from women with PCOS, either induced to ovulate with clomiphene citrate or from a modeled secretory phase using daily administration of progesterone.
  
  
  METHODS
  Total RNA was isolated from samples and processed for array hybridization with Affymetrix HG U133 Plus 2 arrays. Data were analyzed using GeneSpring GX11 and Ingenuity Pathways Analysis. Selected gene expression differences were validated using RT-PCR and/or immunohistochemistry in separately obtained PCOS and normal endometrium.
  
  
  RESULTS
  ANOVA analysis revealed 5160 significantly different genes among the three conditions. Of these, 466 were differentially regulated between fertile controls and PCOS. Progesterone-regulated genes, including mitogen-inducible gene 6 (MIG6), leukemia inhibitory factor (LIF), GRB2-associated binding protein 1 (GAB1), S100P, and claudin-4 were significantly lower in PCOS endometrium; whereas cell proliferation genes, such as Anillin and cyclin B1, were up-regulated.
  
  
  CONCLUSIONS
  Differences in gene expression provide evidence of progesterone resistance in midsecretory PCOS endometrium, independent of clomiphene citrate and corresponding to the observed phenotypes of hyperplasia, cancer, and poor reproductive outcomes in this group of women.
authors.affiliation: Departamento de Ginecologia e Obstetrícia, Programa de Pós-Graduação em Cirurgia: Ciências Cirúrgicas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Brazil.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Savaris
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Groll
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
authors.forename: Franco J
authors.initials: FJ
authors.lastname: DeMayo
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Amy E
authors.initials: AE
authors.lastname: Hamilton
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D002996:Clomiphene / Q000494:pharmacology / Q000627:therapeutic use*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D025341:Principal Component Analysis; D011374:Progesterone / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002996:Clomiphene; D011374:Progesterone