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Placental methylation arrays for the assessment of epigenetic regulation in transcriptional subtypes of human preeclampsia

ABSTRACT: Preeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We recently identified five clusters of placentas within a large gene expression microarray dataset (N=330, GSE75010), of which four contained a substantial number of PE samples. However, while transcriptional analysis of placentas can subtype patients, we hypothesized that the addition of epigenetic information should reveal gene regulatory mechanisms behind the distinct PE pathologies. We, therefore, subjected 48 of our samples to Infinium Human Methylation 450K arrays and investigated relationships between the gene expression and DNA methylation data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98224 | GEO | 2018/03/07

REPOSITORIES: GEO

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Placental gene expression profiling for the identification of clinically relevant subclasses of human preeclampsia

Project description:Preeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We hypothesized that this heterogeneity is due to the existence of multiple molecular forms of PE. To address our hypothesis, we created a large (N=330) human placental microarray data set consisting of seven previously published studies (GSE30186, GSE10588, GSE24129, GSE25906, GSE43942, GSE4707, and GSE44711) and 157 highly annotated samples from a BioBank (below). Applying unsupervised clustering to this combined data set revealed multiple distinct molecular groups of placentas, including three clinically relevant potential origins of PE based on gene expression and correlating patient records.

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NEXT GENERATION SEQUENCING DETECTS DYSREGULATED PLACENTAL MICRORNAS IN PREECLAMPSIA

Project description:Introduction: To determine the miRNA expression profile in pregnancies complicated by Preeclampsia (PE) and compare it to uncomplicated pregnancies. Methods: Seventeen placentas from women with PE, [all of them being late onset PE (LOPE)], as well as 17 placentas from uncomplicated pregnancies were analyzed using miRNA NGS. For statistical analyses the MATLAB® simulation environment was applied. The expression of miR-99b and miR-23b were verified using Quantitative Real-Time Polymerase Chain Reaction. Results: Two miRNAs were found dysregulated in PE complicated placentas. Statistical analysis revealed that miR-99b and miR-23b were under-expressed in complicated placentas as compared to controls. Discussion: Since specific miRNAs can differentiate complicated from uncomplicated pregnancies, they may be considered as putative PE-specific biomarkers.

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Project description:Introduction: To determine the miRNA expression profile in placentas complicated by Preeclampsia (PE) and compare it to uncomplicated pregnancies. Methods: Sixteen placentas from women with PE, including 11 with early onset PE (EOPE) and 5 with late onset PE (LOPE), as well as 8 from uncomplicated pregnancies were analyzed using miRNA microarrays. For statistical analyses the MATLAB® simulation environment was applied. The over-expression of miR-518a-5p was verified using Quantitative Real-Time Polymerase Chain Reaction. Results: Overall, 44 miRNAs were found deregulateddysregulated in PE complicated placentas. Statistical analysis revealed that miR-431, miR-518a-5p and miR-124* were over-expressed in EOPE complicated placentas as compared to controls whereas miR-544 and miR-3942 were down-regulated in EOPE. When comparing the miRNA expression profile in cases with PE and PE- growth restricted fetuses (FGR), miR-431 and miR-518a-5p were found over-expressed in pregnancies complicated by FGR. Additionally, up- regulation of miR-124, miR-423-3p and miR-518a-5p was associated with proteinuria. Discussion: Specific miRNAs can differentiate EOPE and LOPE from uncomplicated pregnancies representing putative PE-specific diagnostic biomarkers. Among them, miR-518a-5p emerged as a potential diagnostic indicator for EOPE cases as well as for FGR and proteinuria associated PE complicated placentas designating its potential link to the severity of the disease.

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Placental Immune alterations in early-onset preeclampsia and late-onset preeclampsia

Project description:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.

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2021-06-12 | GSE177049 | GEO

Epigenome analysis of normal and preeclamptic placenta samples

Project description:Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n=14), with term PE (≥37 weeks; n=19) or with preterm PE (<37 weeks, n=12). Of the 485,582 gene loci on the array, compared to controls, 229 loci were differentially methylated in PE placentas and 3411 loci were differentially methylated in preterm PE (step up p-value <0.05 and >5% methylation difference). Functional annotation of the differentially methylated genes in preterm PE placentas revealed a 32 gene cluster in the cadherin and cell adhesion functional groups (Benjamini p<0.00001). Hypermethylation of CDH11 (p=0.0143), COL5A1 (p=0.0127) and TNF (p=0.0098) and hypomethylation of NCAM1 (p=0.0158) was associated with altered mRNA expression in preterm PE placentas. These studies demonstrate aberrant methylation, correlating with disease severity, in PE placentas. Bisulphite converted DNA from the 45 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2

2014-05-20 | E-GEOD-57767 | biostudies-arrayexpress

Placental gene expression in severe preeclampsia.

Project description:The series is composed of thirty hybridizations for analysis of differentially expressed genes in normal placenta tissues from patients with normal labor and placenta tissues from patients with severe preeclampsia. Patients tissues samples were obtained from (Vasilis. Total RNA extraction was performed by using the MagNa Pure Compact RNA Isolation Kit (Roche Applied Science). Keywords: Gene expression study, Disease state Twenty-six out of 50 normal placentas were randomly selected to match with 17 preeclamptic placentas, accounting for parity. Microarrays were performed applying a direct comparison design.

2010-05-26 | E-GEOD-10588 | biostudies-arrayexpress

Preeclampsia: the in vivo milieu leads to cytotrophoblast dysregulation

Project description:During human pregnancy, placental cytotrophoblasts invade the uterus and its blood vessels, anchoring the progeny and rerouting maternal blood to the embryo/fetus. In preeclampsia, cytotrophoblast invasion is restricted and blood flow to the placenta is reduced. The causes of restricted cytotrophoblast invasion are unknown. Here, preeclampsia and control cytotrophoblasts were cultured for 48 h to allow differentiation/invasion. In various severe forms of preeclampsia Â± intrauterine growth restriction, global transcriptional profiling revealed common aberrations in cytotrophoblast gene expression that resolved with culture. Villous cytotrophoblasts were isolated from preeclampsia placentas (PRE, n=5) and placentas of preterm labor patients without signs of infection (PTL, n=5), which served as gestation-matched controls. To better understand the CTB phenotype in the context of PE variants, we included patients with the most clinically significant forms of this condition that necessitated preterm delivery: women with severe PE Â± intrauterine growth restrictions, PE with superimposed hypertension and HELLP syndrome (hemolysis, elevated liver enzymes; low platelet count). RNA was purified immediately after the cells were isolated (0 h) and after 12, 24 and 48 h in culture. The relative gene expression across the whole genome was profiled using the Affymetrix HG-U133Plus 2.0 GeneChip platform. Array quality was assesed using RMAExpress. One sample of preterm labor collected at 48h was omitted (39 arrays total). We used both LIMMA and maSigPro (R/Bioconductor) to determine differentially expressed genes.

2012-08-17 | E-GEOD-40182 | biostudies-arrayexpress

Gene expression in Early-Onset Preeclampsia Placentas and Controls

Project description:We investigated the DNA methylation and gene expression of 20 chorionic villi samples from early onset preeclampsia placentas to 20 gestational age matched controls. From this we were able to see a widespread disregulation in DNA methylation across a subset of genes in the genome. This may help to elucidate the underlying biological problems that lead to early onset preeclampsia. We noted that there were DNA methylation changes in many genes of importance as well as in different genomic elements such as enhancers. RNA from 8 Early Onset Preeclampsia placentas and 8 gestational age matched controls

2013-06-21 | E-GEOD-44711 | biostudies-arrayexpress

Genome-wide analysis of placental gene expression in severe preterm preeclampsia

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