Nandi Anindita A, Wadhwani Nisha S, Joshi Sadhana R
Department of Nutritional Medicine, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth Deemed University, Pune 411043, India.
Department of Nutritional Medicine, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth Deemed University, Pune 411043, India.
Med Hypotheses. 2017 Mar;100:31-36. doi: 10.1016/j.mehy.2017.01.009. Epub 2017 Jan 17.
Sub-optimal maternal nutrition may result in pregnancy complications like preeclampsia. Preeclampsia is known to be of placental origin and a major cause of maternal morbidity and mortality worldwide. Our earlier studies suggest that altered metabolism of folic acid, vitamin B and long chain polyunsaturated fatty acid (LCPUFAs) in the one carbon cycle increases homocysteine levels in preeclampsia. Recent reports indicate that vitamin D deficiency may also have a role in preeclampsia, although the mechanisms are unclear. A disturbed one carbon cycle can influence methylation patterns of various genes involved in placental development. Altered expression of cystathionine beta synthase (CBS) gene can result in hyperhomocystenemia. Higher homocysteine levels are known to increase reactive oxygen species (ROS) production which in turn leads to increased expression of phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2). Higher expression of PLA2 and COX-2 can influence the release of arachidonic acid (AA) from membrane phospholipid and result in increased conversion to thromboxane. Vitamin D [1,25(OH)D] is known to induce the CBS gene expression while it can suppress the oxidative stress-induced COX-2 up-regulation and thromboxane production. Based on this, we propose a novel hypothesis that a disturbed vitamin D and LCPUFA metabolism influence the regulation of the one carbon cycle which will trigger inflammation through oxidative stress in preeclampsia. This may lead to altered feto-placental growth and development in preeclampsia.
孕产妇营养欠佳可能会导致先兆子痫等妊娠并发症。已知先兆子痫源于胎盘，是全球孕产妇发病和死亡的主要原因。我们早期的研究表明，一碳循环中叶酸、维生素B和长链多不饱和脂肪酸（LCPUFAs）代谢改变会使先兆子痫患者的同型半胱氨酸水平升高。最近的报告表明，维生素D缺乏可能也与先兆子痫有关，尽管其机制尚不清楚。紊乱的一碳循环会影响参与胎盘发育的各种基因的甲基化模式。胱硫醚β合酶（CBS）基因表达改变可导致高同型半胱氨酸血症。已知较高的同型半胱氨酸水平会增加活性氧（ROS）的产生，进而导致磷脂酶A2（PLA2）和环氧化酶-2（COX-2）的表达增加。PLA2和COX-2的高表达会影响花生四烯酸（AA）从膜磷脂中的释放，并导致血栓素转化增加。维生素D [1,25(OH)D] 已知可诱导CBS基因表达，同时它可以抑制氧化应激诱导的COX-2上调和血栓素生成。基于此，我们提出了一个新的假说，即维生素D和LCPUFAs代谢紊乱会影响一碳循环的调节，这将通过先兆子痫中的氧化应激引发炎症。这可能会导致先兆子痫患者胎儿-胎盘生长发育改变。
