Vitamin D metabolism in human pregnancy with an emphasis on the placenta and bone metabolism
Park, Hey Jun
Vitamin D is an essential fat-soluble nutrient that plays a critical role in calcium homeostasis among women of childbearing age. Vitamin D has also been linked to pregnancy health outcomes and may have long-term effects on maternal and child health. Nevertheless, the effects of human pregnancy on vitamin D requirements are poorly understood, and very little is known about placental vitamin D metabolism and its putative effects on maternal circulating pool of vitamin D. The impact of maternal vitamin D status on maternal and fetal bone health is also unclear. As such, my dissertation sought to advance understanding of vitamin D metabolism in human pregnancy, to characterize the effect of the placenta on maternal circulating vitamin D metabolites, and to examine the impact of maternal vitamin D status on maternal and fetal bone health. To achieve these aims, biomarkers of vitamin D status/metabolism were measured in blood and placental tissue obtained from third-trimester pregnant women who participated in a long-term controlled feeding study and consumed equivalent intakes of vitamin D, calcium, and phosphorus. A human placental cell culture model was also used to characterize vitamin D uptake, intracellular metabolism, secretion, and to inform the interpretation of the human study data. The data showed that pregnant women had 30-100% higher (P<0.01) circulating vitamin D metabolites [25(OH)D, 1,25(OH)2D, 3-epi-25(OH)D3, and 25(OH)D:24,25(OH)2D] than nonpregnant women suggesting that the placenta may be a source of vitamin D metabolites during pregnancy. This notion was supported by the significant associations (P<0.04) between maternal circulating vitamin D metabolites and placental mRNA abundance of vitamin D machinery (LRP2, CUBN, CYP2R1, CYP27B1, and CYP24A1), and by the endogenous production and secretion of 25(OH)D3 by placental trophoblasts in vitro. The data also showed that maternal 25(OH)D, free 25(OH)D, 1,25(OH)2D, and epi-25(OH)D3 were inversely associated (P<0.04) with maternal bone resorption markers (deoxypyridinoline, NTx, and iPTH). Overall, these data collectively suggest that pregnancy increases circulating pools of maternal vitamin D metabolites, in part, through the placenta which can produce and secrete all forms of vitamin D metabolites including 25(OH)D3. These findings also imply that achieving higher maternal concentrations of circulating vitamin D metabolites during pregnancy may attenuate maternal bone loss.
Nutrition; 25-hydroxyvitamin D; Bone metabolism; Placenta; Pregnancy; Vitamin D; Endocrinology; Lactation; Molecular biology
Caudill, Marie A.
Mehta, Saurabh; Brannon, Patsy Marie; Antczak, Douglas Francis
PHD of Nutrition
Doctor of Philosophy
dissertation or thesis