Differential placental methylation and expression of VEGF, FLT- 1 and KDR genes in human term and preterm preeclampsia

Sundrani, Deepali; Reddy, Umakar S; Joshi, Anuradha Rajiv; Mehendale, Savita; Chavan‐Gautam, Preeti; Hardikar, Anandwardhan A.; Chandak, Giriraj Ratan; Joshi, Sadhana

doi:10.1186/1868-7083-5-6

Cited by 93 publications

(61 citation statements)

References 49 publications

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“…finding that in EOPE most DMCs were hypomethylated in placental tissue and hypermethylated in UCL and substantiated by other epigenetic studies of candidate genes in PE (Anton et al, 2014;Blair et al, 2013;Hogg et al, 2013;Sundrani et al, 2013;Yuen et al, 2010). The opposite direction of methylation in placental tissue and UCL might be explained by differences in tissue sensitivity and the level of exposure.…”

Section: Discussionsupporting

confidence: 58%

Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues

Berg

Chaves

Herzog

et al. 2017

Chronobiology International

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The placenta is important in providing a healthy environment for the fetus and plays a central role in the pathophysiology of preeclampsia (PE). Fetal and placental developments are influenced by epigenetic programming. There is some evidence that PE is controlled to an altered circadian homeostasis. In a nested case-control study embedded in the Rotterdam Periconceptional Cohort, we obtained placental tissue, umbilical cord leukocytes (UCL), and human umbilical venous endothelial cells of 13 early-onset PE, 16 late-onset PE and 83 controls comprising 36 uncomplicated and 47 complicated pregnancies, i.e. 27 fetal growth restricted and 20 spontaneous preterm birth. To investigate the associations between PE and the epigenetics of circadian clock and clockcontrolled genes in placental and newborn tissues, genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation450K BeadChip and a candidate-gene approach using ANCOVA was applied on 939 CpGs of 39 circadian clock and clock-controlled genes. DNA methylation significantly differed in early-onset PE compared with spontaneous preterm birth at 6 CpGs in placental tissue (3. ≤ p ≤ 0.009). No significant associations were shown with late-onset PE between study groups or tissues. The most differentially methylated CpGs showed hypomethylation in placental tissue and hypermethylation in uncomplicated controls. In conclusion, DNA methylation of circadian clock and clock-controlled genes demonstrated most differences in UCL of early-onset PE compared with spontaneous preterm birth. Implications of the tissue-specific variations in epigenetic programming for circadian performance and long-term health need further investigation.

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Section: Discussionsupporting

confidence: 58%

Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues

Berg

Chaves

Herzog

et al. 2017

Chronobiology International

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“…53,54 We have recently reported altered placental VEGF mRNA expression and CpG methylation patterns in women with PE, suggesting that they are influenced by the intrauterine environment. 55 Thus, with all this background, our study highlights the key role that altered angiogenesis in early pregnancy plays in the pathophysiology of PE.…”

Section: Discussionmentioning

confidence: 84%

A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

et al. 2014

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Our earlier studies of preeclampsia (PE) at delivery have demonstrated the alteration of one carbon cycle, reduced placental omega 3 fatty acids, altered circulating levels of angiogenic factors and differential placental gene-specific methylation patterns of angiogenic factors. This study was undertaken to examine changes in the levels of angiogenic factors and angiotensin II type 1 receptor autoantibodies (AT1-AAs) throughout gestation, from early pregnancy until delivery, in women with PE and to examine their association with cord angiogenic factors, blood pressure and infant weight. A total of 81 pregnant women (46 normotensive and 35 with PE) were followed at three different time points during pregnancy: 16-20 weeks (T1), 26-30 weeks (T2) and at the time of delivery (T3). The plasma levels of angiogenic factors and AT1-AAs were determined in the maternal and cord plasma by commercial enzyme-linked immunosorbent assay kits. Maternal plasma levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were lower (P<0.05 for both), whereas soluble fms-like tyrosine kinase-1 (sFlt-1; P<0.05) and the sFlt-1/PlGF ratio (P<0.01) were higher in early pregnancy in the PE group. Maternal plasma AT1-AA levels were higher (P<0.05) at T2 in women with PE. Cord plasma VEGF and soluble kinase insert domain receptor (sKDR) levels were lower (P<0.01 and P<0.05, respectively), whereas AT1-AA levels were higher (P<0.05) in the PE group. Maternal plasma VEGF levels in early pregnancy were positively associated with systolic blood pressure, whereas the sFlt-1/PlGF ratio at T2 was negatively associated with infant weight in the PE group. Low levels of proangiogenic factors (VEGF and PlGF) and high levels of AT1-AAs and antiangiogenic factors (sFlt-1 and sFlt-1/PlGF ratio) are present in the maternal circulation during early gestation in women with PE.

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“…Pathways that have been identified have included trophoblast motility and invasion, angiogenesis, cell adhesion and survival, the renin-angiotensin-aldosterone system, and immune response (8,15,27,31,34). Altered gene expression in preeclampsiaaffected placentas would indicate a role for epigenetic modifications in the development of preeclampsia.…”

mentioning

confidence: 96%

DNA methylation profiles in preeclampsia and healthy control placentas

Yeung

Chiu

Pidsley

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Preeclampsia is a hypertensive disorder of pregnancy that affects 3-5% of all pregnancies. There is evidence to suggest that epigenetic mechanisms, such as DNA methylation, play a role in placental development and function. This study compared DNA methylation profiles of placentas from preeclampsia-affected pregnancies with placentas from healthy pregnancies to identify gene-specific changes in DNA methylation that may contribute to the development of preeclampsia. The methylation status of eight placental biopsies taken from preeclampsia-affected and 16 healthy pregnancies was analyzed using the Illumina Infinium Methylation 450 BeadChip array. Bisulfite pyrosequencing was used to confirm regions found to be differentially methylated between preeclampsia and healthy placentas. A total of 303 differentially methylated regions, 214 hypermethylated and 89 hypomethylated, between preeclampsia cases and controls were identified, after adjusting for gestational age (adjusted P < 0.05). Functional annotation found cell adhesion, wingless type MMTV Integration Site family member 2 (Wnt) signaling pathway, and regulation of transcription were significantly enriched in these gene regions. Hypermethylation of WNT2, sperm equatorial segment protein (SPESP1), NADPH oxidase 5 (NOX5), and activated leukocyte cell adhesion molecule (ALCAM) in preeclampsia placentas was confirmed with pyrosequencing. This study found differences in methylation in gene regions involved in cell signaling (WNT2), fertilization and implantation (SPESP1), reactive oxygen species signaling (NOX5), and cell adhesion (ALCAM). These results build on recently published studies that have reported significant differences in DNA methylation in preeclampsia placentas.

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Differential placental methylation and expression of VEGF, FLT- 1 and KDR genes in human term and preterm preeclampsia

Cited by 93 publications

References 49 publications

Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues

Early- and late-onset preeclampsia and the DNA methylation of circadian clock and clock-controlled genes in placental and newborn tissues

A longitudinal study of circulating angiogenic and antiangiogenic factors and AT1-AA levels in preeclampsia

DNA methylation profiles in preeclampsia and healthy control placentas

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