Maternal vitamin D deficiency impact on LCPUFA and pregnancy outcome associated with alterations in the one carbon metabolism

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.