Park Heyjun, Wood Madeleine R, Malysheva Olga V, Jones Sara, Mehta Saurabh, Brannon Patsy M, Caudill Marie A
Division of Nutritional Sciences, Cornell University, Ithaca, NY.
Division of Nutritional Sciences, Cornell University, Ithaca, NY
Am J Clin Nutr. 2017 Dec;106(6):1439-1448. doi: 10.3945/ajcn.117.153429. Epub 2017 Oct 11.
Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans. This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy. Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes. In placental tissue, 25-hydroxyvitamin D [25(OH)D] was strongly correlated ( = 0.83, < 0.001) with 24,25-dihydroxyvitamin D Moreover, these placental metabolites were strongly correlated ( ≤ 0.85, ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations ( ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 (, also known as megalin) with 25(OH)D and the C3 epimer of 25(OH)D [3-epi-25(OH)D]; cubilin () with 25(OH)D; 25-hydroxylase () with 3-epi-25(OH)D; 24-hydroxylase () with 25(OH)D, 3-epi-25(OH)D, and 1,25-dihydroxyvitamin D [1,25(OH)D]; and 1α-hydroxylase [() with 3-epi-25(OH)D and 1,25(OH)D]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D and higher gene transcript abundance in response to cholecalciferol treatment. The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a -associated increase in 1,25(OH)D] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D, suggest that the placenta may play an active role in modulating the vitamin D metabolite profile in maternal circulation in human pregnancy. This trial was registered at clinicaltrials.gov as NCT03051867.
关于胎盘维生素D代谢及其对人体母体循环中维生素D浓度的影响，目前所知甚少。本研究旨在深化对胎盘维生素D代谢及其在孕期调节母体循环中维生素D代谢产物作用的当前认识。在一项喂养研究中，24名健康孕妇（妊娠26 - 29周）连续10周摄入单一剂量的维生素D（饮食中511 IU/d以及胆钙化醇补充剂）。对胎盘和血液中维生素D代谢产物的浓度以及维生素D代谢途径成分的胎盘信使核糖核酸（mRNA）丰度进行了定量分析。此外，将培养的人滋养层细胞与碳 - 胆钙化醇一起孵育，以检查维生素D代谢产物的细胞内生成和分泌以及靶基因的调控情况。在胎盘组织中，25 - 羟基维生素D [25(OH)D] 与24,25 - 二羟基维生素D高度相关（r = 0.83，P < 0.001）。此外，这些胎盘代谢产物与其母体循环中的各自代谢产物高度相关（r ≤ 0.85，P ≤ 0.04）。在维生素D代谢成分的胎盘mRNA丰度与循环维生素D代谢产物之间也观察到正相关（P ≤ 0.045）[即低密度脂蛋白相关蛋白2（LRP2，也称为巨膜蛋白）与25(OH)D以及25(OH)D的C3差向异构体[3 - epi - 25(OH)D]；内因子（CUBN）与25(OH)D；25 - 羟化酶（CYP2R1）与3 - epi - 25(OH)D；24 - 羟化酶（CYP24A1）与25(OH)D、3 - epi - 25(OH)D以及1,25 - 二羟基维生素D [1,25(OH)D]；以及1α - 羟化酶[CYP27B1]与3 - epi - 25(OH)D和1,25(OH)D]。值得注意的是，滋养层细胞的体外实验表明，胆钙化醇处理后25(OH)D的产生和分泌增加，且基因转录丰度更高。许多胎盘维生素D代谢生物标志物与孕妇循环维生素D代谢产物之间存在众多关联[包括与1,25(OH)D相关的增加]以及滋养层细胞产生和分泌维生素D代谢产物（尤其是25(OH)D）的证据表明，胎盘可能在调节人类孕期母体循环中的维生素D代谢产物谱方面发挥积极作用。该试验在clinicaltrials.gov上注册为NCT03051867。
