Association of maternal vitamin D status with the risk of preeclampsia.

The aim of this study was to examine serum vitamin D concentrations from early pregnancy until delivery in women who did and did not develop preeclampsia. This longitudinal study was carried out in Pune, India. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from two hospitals.

Hypoxia Inducible Factors (HIF1α and HIF3α) are differentially methylated in preeclampsia placentae and are associated with birth outcomes.

Preeclampsia is a placental vascular pathology and hypoxia is known to influence placental angiogenesis. Hypoxia Inducible Factors (HIF1α and HIF3α) mediate the response to cellular oxygen concentration and bind to hypoxia response element of target genes. However the mechanism regulating above activity is not well-understood.

Longitudinal Assessment of Calcium and Magnesium Levels in Women with Preeclampsia.

The present study reports the levels of maternal serum calcium and magnesium from early pregnancy until delivery, along with cord levels, in women who developed preeclampsia (PE) and compares them with those without PE. A total of 324 pregnant women (216 non-PE and 108 PE women) were included in this retrospective case-control study of prospectively collected data nested in an observational cohort study. Maternal blood was collected at 4 time points during pregnancy (V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery) and umbilical cord blood at delivery.

Association of placental fatty acid desaturase 2 (FADS2) methylation with maternal fatty acid levels in women with preeclampsia.

Introduction: Biosynthesis of long-chain polyunsaturated fatty acids requires sequential activities of desaturases and elongases for conversion of fatty acid precursors to products. The delta-6 desaturase enzyme, encoded by FADS2 gene, is a rate limiting enzyme in this pathway. Alterations in D6D enzyme activity can lead to altered fatty acid profiles.

Placental growth factor and Fms related tyrosine kinase-1 are hypomethylated in preeclampsia placentae.

This study aims to examine the DNA methylation (DNAm) and expression patterns of genes associated with placental angiogenesis in preeclampsia. DNAm and expression were examined in normotensive (n = 100) and preeclampsia (n = 100) women using pyrosequencing and quantitative real-time PCR respectively. Hypomethylation at several CpGs was observed in and in women with preeclampsia compared to normotensive controls.

Region-specific changes in the mRNA and protein expression of LCPUFA biosynthesis enzymes and transporters in the placentae of women with preeclampsia.

Unlabelled: The biosynthesis and transport of long chain polyunsaturated fatty acids (LCPUFA) require the activity of fatty acid desaturase (FADS) enzymes, fatty acid transport proteins (FATP) and fatty acid binding proteins (FABP). In a previous study we have demonstrated region-specific changes in the LCPUFA levels in preeclampsia (PE) as compared to the normotensive control (NC) placentae.

Aim: To understand the region-specific changes in the mRNA levels and protein expression of biosynthesis enzymes and transporters of LCPUFA in PE and NC placentae.

The REVAMP study: research exploring various aspects and mechanisms in preeclampsia: study protocol.

Background: Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the potential for dietary long chain polyunsaturated fatty acids (LCPUFA) as a therapeutic intervention to prevent preeclampsia, as they are involved in angiogenesis, oxidative stress, and inflammatory pathways.

Higher maternal plasma folate, vitamin B and homocysteine levels in women with preeclampsia.

Micronutrients like vitamin B and folate play an important role in nucleic acid metabolism, cell growth, and are important determinants of fetal growth. The present study examined the levels of maternal and cord plasma folate, vitamin B, homocysteine, and their association with birth outcome in women with preeclampsia (PE). This study includes 450 normotensive control (NC) and 350 women with PE.

Matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases -9 (MMP-9) are differentially expressed in different regions of normal and preeclampsia placentae.

Matrix metalloproteinases (MMPs) are involved in the extracellular matrix (ECM) remodeling during human placentation and parturition and have been shown to be associated with oxidative stress. Placental regional changes in oxygen availability and oxidative stress indices may influence regional differences in expression of MMPs. This study examines the protein and mRNA levels of MMP-2 and MMP-9 in different regions of the placenta in normotensive control (NC) women and women with preeclampsia (PE).

Investigating the expression of MMPs and TIMPs in preterm placenta and role of CpG methylation in regulating MMP-9 expression.

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are crucial to the processes of normal labor and parturition. We have previously reported aberrant protein levels of MMPs in placenta of women delivering preterm as compared to term. In this study, we examine the mRNA levels of MMPs (MMP-1, MMP-2, and MMP-9) and TIMPs (TIMP-1, TIMP-2) in the placenta from women delivering preterm as compared with term and further study the promoter DNA methylation of the MMP-9 gene in a sub-sample of term and preterm placentae.

VEGF and VEGFR1 levels in different regions of the normal and preeclampsia placentae.

Altered placental angiogenesis is implicated in the pathophysiology of preeclampsia. We have earlier reported placental regional differences in oxidative stress markers and neurotrophins. Oxidative stress and neurotrophins are reported to regulate angiogenesis.

Hypermethylated CpG sites in the MTR gene promoter in preterm placenta.

Aim: Altered maternal one-carbon metabolism influences placental DNA methylation patterns and 'programs' the fetus for noncommunicable diseases in adult life.

Experimental Procedures: Levels of plasma folate, vitamin B, homocysteine, mRNA and protein levels of MTHFR and MTR enzymes in placenta were compared among women delivering preterm (n = 83) and term (n = 75). MTR promoter CpG methylation was undertaken.

Tubulointerstitial nephritis antigen-like 1 protein is downregulated in the placenta of pre-eclamptic women.

Background: Tubulointerstitial nephritis antigen-like 1 protein (TINAGL1), is a matricellular protein, known to play role in cell adhesion and cell receptor interaction. Research related to TINAGL1 is limited to cell culture and animal models. Demonstration of TINAGL1 as a positive regulator of angiogenesis and its expression in the decidua of postimplantation mouse uterus, prompted us to validate its expression in human placenta during impaired angiogenesis in pre-eclamptic condition.

Placental Proteomics Provides Insights into Pathophysiology of Pre-Eclampsia and Predicts Possible Markers in Plasma.

Pre-eclampsia is a hypertensive disorder characterized by the new onset of hypertension >140/90 mmHg and proteinuria after the 20th week of gestation. The disorder is multifactorial and originates with abnormal placentation. Comparison of the placental proteome of normotensive (n = 25) and pre-eclamptic (n = 25) patients by gel-free proteomic techniques identified a total of 2145 proteins in the placenta of which 180 were differentially expressed (>1.

Altered breast milk components in preeclampsia; An in-vitro proton NMR spectroscopy study.

Objective: To investigate the metabolic profile of milk on day 3 and at the 6th month of lactation in mothers with preeclampsia (PE) and normotensive mothers.

Study Design: Women with PE (n=29) and control women (n=31) were recruited for this study. Milk was collected on day 3 and at the 6th month of lactation.

Variable Methylation Potential in Preterm Placenta: Implication for Epigenetic Programming of the Offspring.

Children born preterm are reported to be at increased risk of developing noncommunicable diseases in later life. Altered placental DNA methylation patterns are implicated in fetal programming of adult diseases. Our earlier animal studies focus on micronutrients (folic acid, vitamin B) and long-chain polyunsaturated fatty acids (LCPUFAs) that interact in the 1 carbon cycle, thereby influencing methylation reactions.

Placental DHA and mRNA levels of PPARγ and LXRα and their relationship to birth weight.

Background: A very large number of fatty acids play wide range of physiological roles in cellular growth and function in placental as well as fetal growth. However, docosahexaenoic acid (DHA), in addition to its critical role in cellular membranes, is known to act as a ligand for several nuclear receptors and regulates the activity of transcription factor families like peroxisome proliferator-activated receptor, liver X receptor (LXR), retinoid X receptor (RXR), and sterol regulatory element binding protein (SREBP). These transcription factors and DHA are known to regulate the placental and fetal growth and development.

Increased oxidative stress from early pregnancy in women who develop preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder, defined as new onset of maternal hypertension and proteinuria after 20 weeks of gestation. Our earlier study has shown increased maternal oxidative stress at delivery to be associated with poor birth outcome in PE. However, these results were observed when the pathology had progressed and may have been secondary to the effects of the disorder.

Maternal Fatty Acids and Their Association with Birth Outcome: A Prospective Study.

Maternal nutrition, especially LCPUFA, is an important factor in determining fetal growth and development. Our earlier cross sectional study reports lower docosahexanoic acid (DHA) levels at the time of delivery in mothers delivering low birth weight (LBW) babies. This study was undertaken to examine the role of the maternal omega-3 and omega-6 fatty acid profile across the gestation in fetal growth.

Differential regional fatty acid distribution in normotensive and preeclampsia placenta.

Background: Long chain polyunsaturated fatty acids (LCPUFAs) are biologically active fatty acids which regulate placental angiogenesis, inflammation, and oxidative stress. Abnormalities in these aspects have been associated with preeclampsia (PE). Further, placenta has a heterogeneous structure with differential vascularization across different regions.

Reduced Maternal Erythrocyte Long Chain Polyunsaturated Fatty Acids Exist in Early Pregnancy in Preeclampsia.

The present prospective study examines proportions of maternal erythrocyte fatty acids across gestation and their association with cord erythrocyte fatty acids in normotensive control (NC) and preeclamptic pregnancies. We hypothesize that maternal fatty acid status in early pregnancy influences fetal fatty acid stores in preeclampsia. 137 NC women and 58 women with preeclampsia were included in this study.

Increased homocysteine levels exist in women with preeclampsia from early pregnancy.

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).

Maternal nerve growth factor levels during pregnancy in women with preeclampsia: A longitudinal study.

Preeclampsia (PE) is characterized by hypertension and proteinuria. Improper development of the placenta due to altered angiogenesis is the main culprit in PE. Nerve growth factor (NGF) is an angiogenic factor which is expressed and localized in the placenta.

Regional differences in the placental levels of oxidative stress markers in pre-eclampsia.

Objective: To examine placental malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) levels in four placental regions among women with and without pre-eclampsia.

Methods: A cross-sectional study was conducted among women aged 18-35 years with a singleton pregnancy in Pune, India, between May 3, 2013, and June 16, 2014. Three groups were enrolled: normotensive; pre-eclampsia, delivered at term; and pre-eclampsia, delivered preterm.