title: GDM Alters Expression of Placental Estrogen Receptor α in a Cell Type and Gender-Specific Manner.
abstract: OBJECTIVE
  The nuclear receptor estrogen receptor α (ERα) is one of the key players in energy balance, insulin resistance, and trophoblast differentiation. We tested the hypothesis that gestational diabetes mellitus (GDM) alters expression of placental ERα in a cell type-specific manner and that this regulation may involve epigenetic changes.
  
  
  METHODS
  Expression of ERα was analyzed by immunohistochemistry using the semiquantitative immunoreactive score in 80 placentas (40 GDM/40 controls). Quantitative real-time polymerase chain reaction (PCR) measured ERα messenger RNA (mRNA) in decidual tissue. Methylation-specific PCR was performed to analyze cytosine-phosphatidyl-guanine-island methylation of the ERα promoter.
  
  
  RESULTS
  Expression of ERα protein is upregulated (P = .011) in GDM in extravillous trophoblasts but not in syncytiotrophoblast. Gestational diabetes mellitus downregulated ERα in decidual vessels only in pregnancies with male but not female fetuses. Furthermore, mRNA of the ERα encoding gene estrogen receptor gene 1 (ESR1) was increased (+1.77 fold) in GDM decidua when compared to controls (P = .024). In parallel, the promoter of ESR1 was methylated only in decidua of healthy control individuals but not in GDM.
  
  
  CONCLUSIONS
  Gestational diabetes mellitus affects expression of placental ERα in a cell type-dependent way, on epigenetic level. These data link GDM with epigenetic deregulations of ERα expression and open new insights into the intrauterine programming hypothesis of GDM.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Klinik Hallerwiese, Department of Obstetrics, Nuremberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Knabl
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, Medical University Graz, Graz, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Hiden
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hüttenbrenner
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Institut für Soziale Pädiatrie und Jugendmedizin, Ludwig-Maximilians-Universität München, Munich, Gemany.
authors.forename: Christina
authors.initials: C
authors.lastname: Riedel
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hutter
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Kirn
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Günthner-Biller
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Department of Obstetrics and Gynecology, Medical University Graz, Graz, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany Klinik Hallerwiese, Department of Obstetrics, Nuremberg, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Kainer
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig Maximilians Universität München, Campus Innenstadt, Munich, Germany udo.jeschke@med.uni-muenchen.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
mesh_terms: D000328:Adult; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D010920:Placenta / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019849:Sex Determination Processes; D012737:Sex Factors; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger
keywords: estrogen; gestational diabetes; methylation; nuclear receptor; trophoblast