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Knabl, J; Hüttenbrenner, R; Hutter, S; Günthner-Biller, M; Riedel, C; Hiden, U; Kainer, F; Desoye, G; Jeschke, U.
Gestational diabetes mellitus upregulates vitamin D receptor in extravillous trophoblasts and fetoplacental endothelial cells.
Reprod Sci. 2015; 22(3):358-366
Doi: 10.1177/1933719114542020
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- Co-Autor*innen der Med Uni Graz
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Desoye Gernot
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Hiden Ursula
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- Abstract:
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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.
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).
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.
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.
© The Author(s) 2014.
- Find related publications in this database (using NLM MeSH Indexing)
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Adult -
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Calcitriol - pharmacology
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Case-Control Studies -
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Cell Line, Tumor -
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Diabetes, Gestational - genetics
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Diabetes, Gestational - metabolism
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Dose-Response Relationship, Drug -
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Endothelial Cells - drug effects
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Endothelial Cells - metabolism
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Female -
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Humans -
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Placenta - blood supply
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Pregnancy -
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RNA, Messenger - metabolism
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Receptors, Calcitriol - agonists
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Receptors, Calcitriol - genetics
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Receptors, Calcitriol - metabolism
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Trophoblasts - drug effects
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Trophoblasts - metabolism
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Up-Regulation -
- Find related publications in this database (Keywords)
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gestational diabetes mellitus
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vitamin D receptor
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nuclear receptor
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trophoblasts