Schulz Elizabeth V, Cruze Lori, Wei Wei, Gehris John, Wagner Carol L
Departments of Pediatrics, 169 Ashley Avenue, Charleston, SC, 29425, USA.
OB/GYN, 169 Ashley Avenue, Charleston, SC, 29425, USA.
J Steroid Biochem Mol Biol. 2017 Oct;173:273-279. doi: 10.1016/j.jsbmb.2017.02.003. Epub 2017 Feb 13.
Maternal circulating 25-hydroxyvitamin D [25(OH)D] has been shown to optimize production of 1,25-dihydroxyvitamin D [1,25(OH)D] 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.
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 D 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.
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.
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 D supplementation on gene transcription in the placenta, thereby potentially decreasing antiangiogenic factors that may contribute to vascular pregnancy complications.
孕妇循环中的25-羟维生素D[25(OH)D]已被证明在孕期约100纳摩尔/升时可优化1,25-二羟维生素D[1,25(OH)D]的生成，这对胎儿健康结局有显著影响。此外，孕妇25(OH)D浓度低与血管性妊娠并发症（如先兆子痫）之间存在关联。为了进一步阐明维生素D活性在孕期的作用，我们研究了孕妇25(OH)D（维生素D状态的营养指标）在胎盘维持方面的作用，特别是与血管生成和维生素D代谢相关的胎盘基因靶点的表达。
对43名参与一项随机对照试验的受试者的胎盘进行了聚焦分析，该试验在孕期每天补充400国际单位或4400国际单位的维生素D。胎盘mRNA在分娩后一小时内从活检组织中分离出来，随后进行定量PCR。我们将循环浓度<100纳摩尔/升的孕妇归类为缺乏，将≥100纳摩尔/升的孕妇归类为充足。基于双样本Wilcoxon检验，将每个基因在PCR循环阈值（ΔCT）中的变化值（这是靶标浓度的相对测量值）与孕妇25(OH)D浓度<100纳摩尔/升和≥100纳摩尔/升进行比较。
与循环25(OH)D<100纳克/毫升的亚组相比，循环25(OH)D≥100纳克/毫升的孕妇亚组中可溶性FMS样酪氨酸激酶1（sFlt-1）和血管内皮生长因子（VEGF）基因表达显著下调。
在此，我们报告了孕妇维生素D状态与mRNA水平上sFlt-1和VEGF表达之间的显著关联。孕妇循环25(OH)D≥100纳摩尔/升表明孕妇补充维生素D对胎盘基因转录有影响，从而可能减少可能导致血管性妊娠并发症的抗血管生成因子。
