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Gestational Diabetes Mellitus Upregulates Vitamin D Receptor in Extravillous Trophoblasts and Fetoplacental Endothelial Cells

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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.

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Authors and Affiliations

  1. Department of Gynaecology and Obstetrics, Campus Innenstadt, Ludwig-Maximilian-University Munich, Maistrasse 11, D-80337, Munich, Germany

    Julia Knabl MD, Rebecca Hüttenbrenner, Stefan Hutter MD, Maria Günthner-Biller MD, Christina Riedel MSc, Ursula Hiden PhD, Franz Kainer MD, Gernot Desoye PhD & Udo Jeschke PhD

  2. Institut für Soziale Pädiatrie und Jugendmedizin, Ludwig-Maximilians-Universität München, Munich, Germany

    Christina Riedel MSc

  3. Department of Obstetrics and Gynecology, Medical University Graz, Graz, Austria

    Ursula Hiden PhD & Gernot Desoye PhD

Authors
  1. Julia Knabl MD
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  2. Rebecca Hüttenbrenner
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  3. Stefan Hutter MD
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  4. Maria Günthner-Biller MD
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  6. Ursula Hiden PhD
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  9. Udo Jeschke PhD
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Correspondence to Udo Jeschke PhD.

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Knabl, J., Hüttenbrenner, R., Hutter, S. et al. Gestational Diabetes Mellitus Upregulates Vitamin D Receptor in Extravillous Trophoblasts and Fetoplacental Endothelial Cells. Reprod. Sci. 22, 358–366 (2015). https://doi.org/10.1177/1933719114542020

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