Nisha Wadhwani

Altered maternal proportions of long chain polyunsaturated fatty acids and their transport leads to disturbed fetal stores in preeclampsia

Our previous cross-sectional studies have shown altered proportions of long chain polyunsaturated fatty acids (LCPUFA) in preeclampsia (PE) at the end of pregnancy when the pathology has already progressed. The present longitudinal study for the first time reports fatty acid proportions from 16th week of gestation till delivery and placental transport in PE. This is a hospital based study where women were recruited in early pregnancy. Maternal blood was collected at 3 time points i.e. T1=16-20th week, T2=26-30th week and T3=at delivery. Cord blood and placenta were collected at delivery. This study reports data on 140 normotensive control (NC) and 54 PE women. In PE we report lower proportions of DHA in maternal plasma at T1, cord plasma and placenta (p<0.05 for all). The mRNA levels of placental ∆5 desaturase, fatty acid transport proteins -1, -4, were lower (p<0.05 for all) in PE. There was also a positive association between cord and maternal plasma DHA and total omega-3 fatty acids at T1. This study demonstrates that women with PE have lower fatty acids stores at 16-20th week of gestation and lower placental synthesis and transport. It is likely that supplementation of omega-3 fatty acids during the 16-20th week of gestation may help in improving fatty acid status in infants born to mothers with PE.

Reduced levels of placental long chain polyunsaturated fatty acids in preterm deliveries

Reports suggest that the placenta in preterm birth may provide clues to predicting the risk of individuals developing chronic diseases in later life. Placental delivery of long chain polyunsaturated fatty acids (LCPUFA) (constituents of the cell membrane and precursors of prostaglandins) is essential for the optimal development of the central nervous system of the fetus. The present study examines the levels of LCPUFA and their association with placental weight and birth outcome in 58 women delivering preterm and 44 women delivering at term. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels were lower (p<0.01) in women delivering preterm. There was a positive association of placental DHA with placental weight (p=0.036) and nervonic acid with head circumference (p=0.040) in the preterm group. Altered placental LCPUFA status exists in Indian mothers delivering preterm, which may influence the birth outcome.

Maternal micronutrients and omega 3 fatty acids affect placental fatty acid desaturases and transport proteins in Wistar rats.

Adequate supply of LCPUFA from maternal plasma is crucial for fetal normal growth and development. The present study examines the effect of maternal micronutrients (folic acid and vitamin B12) and omega 3 fatty acids on placental mRNA levels of fatty acid desaturases (Δ5 and Δ6) and transport proteins. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B12. Both the vitamin B12 deficient groups were supplemented with omega 3 fatty acid. Maternal vitamin B12 deficiency reduced placental mRNA and protein levels of Δ5 desaturase, mRNA levels of FATP1 and FATP4 (p<0.05 for all) as compared to control while omega 3 fatty acid supplementation normalized the levels. Our data for the first time indicates that altered maternal micronutrients and omega 3 fatty acids play a key role in regulating fatty acid desaturase and transport protein expression in placenta.

Effect of maternal micronutrients (folic acid, vitamin B12) and omega 3 fatty acids on liver fatty acid desaturases and transport proteins in Wistar rats

A disturbed fatty acid metabolism increases the risk of adult non-communicable diseases. This study examines the effect of maternal micronutrients on the fatty acid composition, desaturase activity, mRNA levels of fatty acid desaturases and transport proteins in the liver. Pregnant female rats were divided into 6 groups at 2 levels of folic acid both in the presence and absence of vitamin B(12). The vitamin B(12) deficient groups were supplemented with omega 3 fatty acid. An imbalance of maternal micronutrients reduces liver docosahexaenoic acid, increases Δ5 desaturase activity but decreases mRNA levels, decreases Δ6 desaturase activity but not mRNA levels as compared to control. mRNA level of Δ5 desaturase reverts back to the levels of the control group as a result of omega 3 fatty acid supplementation. Our data for the first time indicates that maternal micronutrients differentially alter the activity and expression of fatty acid desaturases in the liver.

Altered development and function of the placental regions in preeclampsia and its association with long-chain polyunsaturated fatty acids

The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long‐chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582–597. doi: 10.1002/wdev.238

Increased homocysteine levels exist in women with preeclampsia from early pregnancy

Abstract Objective: The present prospective study examines the levels of maternal plasma folate, vitamin B12 and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery. Methods: The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1 = 16th–20th weeks, T2 = 26th–30th weeks and T3 = at delivery). Levels of folate, vitamin B12 and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology. Results: Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B12 levels were significantly higher in PE (p < 0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p < 0.05 for both) and T3 (p < 0.01). Conclusion: Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.

Altered metabolic homeostasis between vitamin D and long chain polyunsaturated fatty acids in preeclampsia

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 B12 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)2D3] 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.