thromboxane-b2 and Vitamin-D-Deficiency

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 pro-inflammatory 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 LCPUFA metabolites and contribute to placental inflammation and endothelial dysfunction in preeclampsia.

Topics: Adolescent; Adult; Cross-Sectional Studies; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Infant, Newborn; Malondialdehyde; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Receptors, Calcitriol; Thromboxane B2; Vitamin D; Vitamin D Deficiency; Young Adult

This study aims to test the hypothesis that vitamin D deficiency can influence long-chain polyunsaturated fatty acid metabolism through alterations in the one-carbon cycle. Wistar rats (n = 8 per group) were given either a control (1,000 IU D3/kg diet) or a vitamin D deficient (VDD) (0 IU D3/kg diet) diet from pre-pregnancy to delivery. On day 20 of gestation, pregnant female rats were delivered by C-section to collect placenta and blood. VDD group demonstrated high serum parathyroid hormone, low serum phosphate, low plasma folate, higher plasma homocysteine, and higher plasma malondialdehyde levels (P < 0.05 for all) as compared to control. Lower protein levels of placental cystathionine-β-synthase enzyme (P < 0.05) were observed in the VDD group as compared to control. VDD group demonstrated higher placental mRNA levels of the enzymes phospholipase A

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Calcium; Cyclooxygenase 2; Cystathionine beta-Synthase; Disease Models, Animal; Female; Folic Acid; Gene Expression Regulation; Group II Phospholipases A2; Homocysteine; Humans; Malondialdehyde; Parathyroid Hormone; Phosphates; Placenta; Pregnancy; Rats; Rats, Wistar; Signal Transduction; Thromboxane B2; Vitamin B 12; Vitamin D Deficiency