title: Gestational diabetes mellitus upregulates vitamin D receptor in extravillous trophoblasts and fetoplacental endothelial cells.
abstract: OBJECTIVE
  Gestational diabetes mellitus (GDM) is often accompanied by low maternal vitamin D, that is, calcitriol (1,25[OH]2 vitamin D3), levels. Here, we tested the hypothesis that the placental vitamin D receptor (VDR) is regulated by calcitriol and altered in GDM with distinct changes in different placental cell types. Specifically, we aimed to localize VDR in human term placentas from normal and GDM pregnancies, to quantify its cellular expression and to study in vitro its regulation by its physiological agonist calcitriol.
  
  
  METHODS
  Placental tissue slides of 80 patients (40 with GDM/40 controls) were double stained for VDR and human leukocyte antigen G to identify extravillous trophoblasts (EVTs). Staining intensity was semiquantified. Quantitative real time-polymerase chain reaction and Western blotting measured VDR messenger RNA (mRNA) and protein in decidual tissue. The trophoblast cell line BeWo was used to study in vitro VDR regulation by calcitriol (0.01, 0.1, and 1 nmol/mL).
  
  
  RESULTS
  Vitamin D receptor protein and mRNA levels are upregulated (P < .05) in EVT (1.8-fold) as well as in placental endothelium (5.8-fold) of patients with GDM. Expression of VDR is regulated by calcitriol in a bimodal manner: high doses (0.1 and 1 nmol/mL) caused downregulation, whereas the low dose (0.01 nmol/mL) resulted in VDR upregulation.
  
  
  CONCLUSIONS
  Vitamin D receptor is upregulated in EVT and endothelium of GDM placentas. This could be due to low maternal vitamin D levels in patients with GDM because in vitro low calcitriol doses upregulate VDR in trophoblast cells.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Knabl
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hüttenbrenner
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hutter
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Günthner-Biller
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany Institut für Soziale Pädiatrie und Jugendmedizin, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Riedel
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, 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, Munich, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Kainer
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, 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, Munich, Germany udo.jeschke@med.uni-muenchen.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016640:Diabetes, Gestational / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D018167:Receptors, Calcitriol; C579457:VDR protein, human; D002117:Calcitriol
keywords: gestational diabetes mellitus; nuclear receptor; trophoblasts; vitamin D receptor