Julia Knabl1, Rebecca Hüttenbrenner1, Stefan Hutter1, Maria Günthner-Biller1, Christina Riedel2, Ursula Hiden3, Franz Kainer1, Gernot Desoye3, Udo Jeschke4. 1. Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany. 2. Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany Institut für Soziale Pädiatrie und Jugendmedizin, Ludwig-Maximilians-Universität München, Munich, Germany. 3. Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany Department of Obstetrics and Gynecology, Medical University Graz, Graz, Austria. 4. Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universität, Munich, Germany udo.jeschke@med.uni-muenchen.de.
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. STUDY DESIGN: 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. CONCLUSION: 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.
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. STUDY DESIGN: 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. CONCLUSION: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: F Pardo; P Arroyo; C Salomón; F Westermeier; R Salsoso; T Sáez; E Guzmán-Gutiérrez; A Leiva; L Sobrevia Journal: Placenta Date: 2013-09-25 Impact factor: 3.481
Authors: Nancy Q Liu; Amber T Kaplan; Venu Lagishetty; Yuxin B Ouyang; Yi Ouyang; Charles F Simmons; Ozlem Equils; Martin Hewison Journal: J Immunol Date: 2011-04-11 Impact factor: 5.422
Authors: Sarah E Bennett; Jennifer McPeake; David R McCance; John G Manderson; Philip Johnston; Rachel McGalliard; Ann McGinty Journal: PLoS One Date: 2013-09-03 Impact factor: 3.240
Authors: Julia Knabl; Aurelia Vattai; Yao Ye; Julia Jueckstock; Stefan Hutter; Franz Kainer; Sven Mahner; Udo Jeschke Journal: Int J Mol Sci Date: 2017-11-06 Impact factor: 5.923
Authors: Julia Knabl; Lena de Maiziere; Rebecca Hüttenbrenner; Stefan Hutter; Julia Jückstock; Sven Mahner; Franz Kainer; Gernot Desoye; Udo Jeschke Journal: Int J Mol Sci Date: 2020-06-05 Impact factor: 5.923