Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women.

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.