Proposing interactions between maternal phospholipids and the one carbon cycle: A novel mechanism influencing the risk for cardiovascular diseases in the offspring in later life
2015
Khot, Vinita | Chavan-Gautam, Preeti | Joshi, Sadhana
Studies have adequately demonstrated the importance of maternal nutrition, particularly, micronutrients (folic acid, vitamin B12) and long chain polyunsaturated fatty acids (LCPUFAs) in determining pregnancy outcome. Reports indicate that children born preterm or to mothers with preeclampsia are at increased risk of developing cardiovascular diseases (CVD) in later life although mechanisms are unclear. Our earlier studies have established that micronutrients (folic acid, vitamin B12) and LCPUFAs are interlinked in the one carbon cycle and influence methylation reactions. Here, we propose a novel hypothesis that altered phospholipid metabolism and dysregulation in the one carbon cycle will result in altered epigenetic programming of placental genes leading to an adverse pregnancy outcome with increased risk of adult diseases in the offspring. Folic acid and vitamin B12 are involved in S-adenosylmethionine (SAM) synthesis, the major methyl donor for most methyl acceptors. Inadequacy of LCPUFA containing phospholipids, one of the major methyl group acceptors in the one carbon metabolic pathway, may cause diversion of methyl groups toward deoxyribonucleic acid (DNA) eventually resulting in aberrant DNA methylation patterns. These modified DNA methylation patterns lead to alterations in the expression of vital genes e.g. angiogenic factor genes thereby contributing to the dysregulation of angiogenesis/vasculogenesis further affecting placental development. This consequently would adversely “program” the fetus for increased risk of CVD in later life.
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