Vitamin D metabolism in pregnant women consuming controlled intakes

 描述（由申请人提供）：尽管越来越多的证据表明维生素D与妊娠期间的孕产妇和胎儿健康结果有关，但对妊娠对维生素D代谢的影响知之甚少。值得注意的是，胎盘正在成为循环母体维生素D代谢物的可能来源和调节剂，因为它表达维生素D代谢途径的所有组分，并且可以产生1，25 [OH]2D，其在生殖状态期间加倍。然而，很少有研究调查胎盘对母体循环维生素D代谢物的调节作用。此外，虽然已知维生素D会影响非妊娠状态下的骨骼健康，但尚不清楚孕妇维生素D状态是否会影响妊娠期间母亲和胎儿的骨骼健康。动物研究表明，严重缺乏维生素D的小鼠胎儿的骨骼健康结果正常，而人类研究的数据可能是混合的，这可能是由于钙，磷和其他影响骨骼健康的营养素的饮食摄入量研究之间的差异。这项研究旨在通过测量一组全面的维生素D生物标志物来促进对妊娠期间维生素D代谢和需求的理解，这些生物标志物来自参与喂养研究并摄入等量维生素D和其他相关营养素的妊娠和非妊娠对照女性。具体目的如下：目的1将检验妊娠改变维生素D代谢的血液生物标志物（包括25（OH）D、1，25（OH）2D、24，25（OH）2D和维生素D结合蛋白（DBP））的假设。目的2将检验胎盘代谢维生素D并促进母体循环维生素D代谢物（包括1，25（OH）2D）变化的假设。为了实现这一目标，我们将测量巨蛋白-cubilin受体、25-羟化酶（CYP 2 R1）、1-羟化酶（CYP 27 B1）和24-羟化酶（CYP 24 A1）的胎盘基因和蛋白表达水平，以及胎盘代谢物25（OH）D、1，25（OH）2D、24，25（OH）2D和DBP的浓度。将检查维生素D的胎盘和母体生物标志物之间的关系，并将采用人胎盘细胞培养模型来研究维生素D代谢通量并指导胎盘组织实验的解释。目的3将检验母体血清25（OH）D水平与母体和胎儿骨代谢标志物相关的假设。为了实现这一目标，我们将检查母体维生素D状态标志物（即，25[OH]D和1，25 [OH]2D）和母体/脐带血中骨健康生化标志物的水平（例如，甲状旁腺激素）。

 DESCRIPTION (provided by applicant): Despite growing evidence linking vitamin D to maternal and fetal health outcomes during pregnancy, little is known about the effect of pregnancy on vitamin D metabolism. Notably, the placenta is emerging as a possible source and regulator of circulating maternal vitamin D metabolites because it expresses all components of the vitamin D metabolic pathway and can produce 1,25[OH]2D which doubles during this reproductive state. Nonetheless, few studies have investigated the modulatory role of the placenta on maternal circulating vitamin D metabolites. In addition, although vitamin D is known to influence bone health in the nonpregnant state, it is unclear whether maternal vitamin D status influences maternal and fetal bone health during pregnancy. Animal studies have shown normal bone health outcomes in fetuses from severely vitamin D deficient mice while data from human studies are mixed possibly due to differences among studies in the dietary intakes of calcium, phosphorous, and other nutrients that impact bone health. This study seeks to advance understanding of vitamin D metabolism and requirements during pregnancy by measuring a comprehensive panel of vitamin D biomarkers from pregnant and nonpregnant control women who participated in a feeding study and consumed equivalent intakes of vitamin D and other related nutrients. The Specific Aims are as follows: Aim 1 will test the hypothesis that pregnancy alters blood biomarkers of vitamin D metabolism including 25(OH)D,1,25(OH)2D, 24,25(OH)2D and vitamin D binding protein (DBP). Aim 2 will test the hypothesis that placenta metabolizes vitamin D and contributes to the changes in maternal circulating vitamin D metabolites including 1,25(OH)2D. To achieve this aim, we will measure placental gene and protein expression levels of the megalin-cubilin receptor, 25-hydroxylase (CYP2R1), 1-hydroxylase (CYP27B1), and 24-hydroxylase (CYP24A1) as well as placental metabolite concentrations of 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and DBP. Relationships between placental and maternal biomarkers of vitamin D will be examined and a human placental cell culture model will be employed to investigate vitamin D metabolic flux and guide interpretation of the placental tissue experiments. Aim 3 will test the hypothesis that maternal serum 25(OH)D levels associate with maternal and fetal markers of bone metabolism. To achieve this aim, we will examine correlations between maternal markers of vitamin D status (i.e., 25[OH]D and 1,25[OH]2D) and maternal/cord blood levels of biochemical markers of bone health (e.g., parathyroid hormone).