Maternal vitamin D sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy

J Steroid Biochem Mol Biol. 2017 Oct;173:273-279. doi: 10.1016/j.jsbmb.2017.02.003. Epub 2017 Feb 13.


Introduction: Maternal circulating 25-hydroxyvitamin D [25(OH)D] has been shown to optimize production of 1,25-dihydroxyvitamin D [1,25(OH)2D] during pregnancy at approximately 100nmoles/L, which has pronounced effects on fetal health outcomes. Additionally, associations are noted between low maternal 25(OH)D concentrations and vascular pregnancy complications, such as preeclampsia. To further elucidate the effects of vitamin D activity in pregnancy, we investigated the role of maternal 25(OH)D, the nutritional indicator of vitamin D status, in relation to placental maintenance and, specifically, expression of placental gene targets related to angiogenesis and vitamin D metabolism.

Methods: A focused analysis of placental mRNA expression related to angiogenesis, pregnancy maintenance, and vitamin D metabolism was conducted in placentas from 43 subjects enrolled in a randomized controlled trial supplementing 400IU or 4400IU of vitamin D3 per day during pregnancy. Placental mRNA was isolated from biopsies within one hour of delivery, followed by quantitative PCR. We classified pregnant women with circulating concentrations of <100nmoles/L as deficient and those with ≥100nmoles/L as sufficient. The value of each gene's change in the PCR cycle threshold (ΔCT), which is a relative measure of target concentration, was compared with maternal 25(OH)D concentrations <100nmoles/L and ≥100nmoles/L based on a two-sample Wilcoxon test.

Results: Soluble FMS-like tyrosine kinase 1 (sFlt-1) and vascular endothelial growth factor (VEGF) gene expression was significantly downregulated in the maternal subgroup with circulating 25(OH)D ≥100ng/mL compared to the subgroup <100ng/mL.

Discussion: Here, we report a significant association between maternal vitamin D status and the expression of sFlt-1 and VEGF at the mRNA level. Achieving maternal circulating 25(OH)D ≥100nmoles/L suggests the impact of maternal vitamin D3 supplementation on gene transcription in the placenta, thereby potentially decreasing antiangiogenic factors that may contribute to vascular pregnancy complications.

Keywords: Placenta; Preeclampsia; Vascular endothelial growth factor; Vitamin D; sFlt-1.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Cholecalciferol / metabolism
  • Cholecalciferol / therapeutic use
  • Comorbidity
  • Down-Regulation*
  • Female
  • Humans
  • Placenta / metabolism*
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism
  • Pregnancy
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Transcriptional Activation
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / metabolism
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / genetics
  • Vitamin D Deficiency / metabolism
  • Vitamins / metabolism
  • Vitamins / therapeutic use
  • Young Adult


  • Biomarkers
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Vitamins
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1