Abstract Preeclampsia is a pregnancy specific disorder, leading to maternal and infant morbidity and mortality. Abnormal placentation has been reported in preeclampsia. Nutrients like vitamin D and long chain polyunsaturated fatty acids (LCPUFA) are known to play a role in placental development. In an animal model we have previously demonstrated that maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio and contributes to inflammation and vasoconstriction. We hypothesize that maternal vitamin D status influences placental LCPUFA metabolism through alterations in one carbon metabolism in women with preeclampsia. To test this hypothesis we recruited 69 normotensive control (NC) women and 50 women with preeclampsia. Women with preeclampsia had lower placental protein and mRNA levels of cystathionine-β-synthase (CBS), higher plasma malondialdehyde (MDA) levels and higher levels of arachidonic acid (AA) and total omega-6 fatty acids in the placenta. Women with preeclampsia also demonstrated higher placental mRNA levels of cyclooxygenase-2 (COX-2) as compared to NC women. Maternal 25(OH)D levels were negatively associated with maternal plasma MDA levels. Placental vitamin D receptor (VDR) levels were positively associated with CBS while maternal MDA levels were positively associated with serum levels of thromboxane-B2 (TXB2) levels. Our findings indicate that vitamin D deficiency increases oxidative stress through alterations in one carbon metabolism to influence proinflammatory omega-6 metabolic pathway in the placenta. This study demonstrates a possible mechanism through which vitamin D deficiency can result in an imbalance in the long chain polyunsaturated fatty acid (LCPUFA) metabolites and contribute to placental inflammation and endothelial dysfunction in preeclampsia.

中文翻译：

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母亲维生素 D 缺乏对 LCPUFA 和与一碳代谢改变相关的妊娠结局的影响

摘要 先兆子痫是一种妊娠特异性疾病，会导致母婴发病率和死亡率。在先兆子痫中已经报道了异常胎盘。众所周知，维生素 D 和长链多不饱和脂肪酸 (LCPUFA) 等营养素在胎盘发育中发挥作用。在动物模型中，我们之前已经证明母体维生素 D 缺乏会增加血栓素/前列环素的比例，并导致炎症和血管收缩。我们假设母体维生素 D 状态通过改变先兆子痫女性的一碳代谢来影响胎盘 LCPUFA 代谢。为了验证这一假设，我们招募了 69 名血压正常对照 (NC) 女性和 50 名患有先兆子痫的女性。患有先兆子痫的女性胎盘蛋白和胱硫醚-β-合酶 (CBS) 的 mRNA 水平较低，胎盘中较高的血浆丙二醛 (MDA) 水平和较高水平的花生四烯酸 (AA) 和总 omega-6 脂肪酸。与 NC 女性相比，先兆子痫女性的胎盘 mRNA 水平也更高。母体 25(OH)D 水平与母体血浆 MDA 水平呈负相关。胎盘维生素 D 受体 (VDR) 水平与 CBS 呈正相关，而母体 MDA 水平与血清​​血栓素 B2 (TXB2) 水平呈正相关。我们的研究结果表明，维生素 D 缺乏会通过改变一碳代谢来影响胎盘中促炎 omega-6 代谢途径，从而增加氧化应激。