Vitamin D deficiency has been associated with preeclampsia, however, vitamin D supplementation studies have shown equivocal data on amelioration of this disease. We hypothesize that women with preeclampsia have an altered endogenous vitamin D homeostasis that counteracts the beneficial effects of vitamin D supplementation. Our study population consisted of 66 maternal/neonate dyads: 16 early-onset (<34 weeks) preeclampsia (EOP), 16 early-onset controls (EOC), 17 late-onset (≥34 weeks) preeclampsia (LOP), and 17 late-onset controls (LOC). Plasma levels of 25-OH-D and the bioactive metabolite 1α,25-(OH)₂-D were studied by ELISA. Placental expression of vitamin D transporters (cubulin and megalin), metabolic genes (CYP2R1, CYP27B1, CYP24A1), and vitamin D binding protein (GC), were studied by real-time PCR, and the nuclear and cytosolic levels of the vitamin D receptor (VDR) protein were analyzed by immunoblotting. Maternal admission, maternal postpartum, and umbilical cord blood levels of 1α,25-(OH)₂-D and placental nuclear vitamin D receptor protein levels, were significantly lower in EOP compared to EOC. In contrast LOP was characterized by lower 25-OH-D levels in maternal postpartum and cord blood, and decreased placental cubulin expression compared to LOC. Both EOP and LOP showed decreased placental expression of CYP2R1 and GC compared to controls. Multivariable linear regression analysis demonstrated that preeclampsia was a significant predictor of decreased 1α,25-(OH)₂-D levels in early-onset subjects, while maternal BMI, but not preeclampsia, was the main predictor of decreased 25-OH-D in late-onset subjects. The highest positive correlation between the two vitamin D metabolites was observed in LOC umbilical cord blood. Finally, paired analysis of maternal metabolites before and after delivery indicated that women without preeclampsia had better maintenance of vitamin D levels. We conclude that EOP is characterized by decreased bioactivation of vitamin D and VDR in association with fetal growth restriction (FGR). In contrast, LOP is characterized by decreased 25-OH-D levels in association with decreased placental CYP2R1 and cubulin expression; and uncoupling of the 25-OH-D with the 1α,25-(OH)₂-D metabolite.

维生素 D 缺乏与先兆子痫有关，但是，补充维生素 D 的研究显示了改善这种疾病的模棱两可的数据。我们假设患有先兆子痫的女性内源性维生素 D 稳态发生了改变，从而抵消了补充维生素 D 的有益作用。我们的研究人群包括 66 名母婴二元组：16 名早发性（<34 周）先兆子痫 (EOP)、16 名早发性对照 (EOC)、17 名迟发性（≥34 周）先兆子痫 (LOP) 和 17迟发控制（LOC）。25-OH-D 和生物活性代谢物 1α,25-(OH) _{2 的}血浆水平-D通过ELISA研究。通过实时 PCR 研究了维生素 D 转运蛋白（cubulin 和巨蛋白）、代谢基因（CYP2R1、CYP27B1、CYP24A1）和维生素 D 结合蛋白 (GC) 的胎盘表达，以及维生素 D 受体的核和细胞溶质水平(VDR) 蛋白通过免疫印迹分析。产妇入院、产后产妇和脐带血 1α,25-(OH) _{2 水平}与 EOC 相比，EOP 中的 -D 和胎盘核维生素 D 受体蛋白水平显着降低。相比之下，与 LOC 相比，LOP 的特征是母体产后和脐带血中 25-OH-D 水平较低，胎盘 cubulin 表达降低。与对照组相比，EOP 和 LOP 均显示 CYP2R1 和 GC 的胎盘表达降低。多变量线性回归分析表明先兆子痫是 1α,25-(OH) ₂降低的重要预测因子早发型受试者的 -D 水平，而母亲 BMI，但不是先兆子痫，是晚发型受试者 25-OH-D 降低的主要预测因素。在 LOC 脐带血中观察到两种维生素 D 代谢物之间的最高正相关性。最后，分娩前后母体代谢物的配对分析表明，没有先兆子痫的女性维生素 D 水平维持得更好。我们得出结论，EOP 的特征是维生素 D 和 VDR 的生物活性降低，与胎儿生长受限 (FGR) 相关。相比之下，LOP 的特点是 25-OH-D 水平降低，同时胎盘 CYP2R1 和 cubulin 表达降低；以及 25-OH-D 与 1α,25-(OH) ₂ -D 代谢物的解偶联。