Early onset preeclampsia (EOPE) in a model for early stage human placental trophoblast
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE119265 | GEO | 2018/12/31
REPOSITORIES: GEO
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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.
2017-09-07 | GSE103542 | GEO
Project description:Preeclampsia (PE) affects 5-8% of pregnancies and has detrimental effects on maternal-fetal health. PE is characterized by de novo hypertension after 20 weeks of gestation and end-organ damage. Systemic inflammatory imbalance has been associated with PE, but its contribution to the pathology is poorly understood. Our objective was to investigate maternal systemic immune changes in early-onset PE (EOPE) and late-onset PE (LOPE) vs uncomplicated pregnancies (CTRL), and their contribution to endothelial activation, hallmark of hypertension. Blood samples were analyzed by flow cytometry, multiplex assay, intracellular cytokine staining (ICS), and single-cell RNA sequencing. We performed co-cultures between circulating immune cells and human umbilical veins endothelial cells (HUVECs) to assess endothelial activation. We found that EOPE had decreased Treg (4.64±0.33, p<0.05) and monocytes (33.92±3.08, p<0.01), whereas LOPE had decreased Treg (4.60±0.30, p<0.05) and Th2 cells (7.50±0.62, p<0.01) vs CTRL. Compared to CTRL, elevated cytokines/chemokines, and growth factors were observed in LOPE, whereas EOPE primarily showed decreased levels. Using ICS, we observed more monocytes producing IL-12, TNF, and IL-1 (all p<0.05) in LOPE vs CTRL. At the transcriptomic level, we found differentially expressed genes (DEGs) between EOPE and CTRL, predominantly related to upregulation of immune activation pathways. Lastly, EOPE peripheral blood mononuclear cells (PBMCs) induced heightened endothelial activation in vitro observed by increased ICAM-1 and ET-1 (p<0.05), whereas LOPE PBMCs required LPS stimulation. While significant proteomic changes are observed in the LOPE group, the EOPE displayed changes mostly at the transcriptomic levels and could induce endothelial activation in vitro.
2024-09-24 | GSE266488 | GEO
Project description:Introduction. Preeclampsia (PE) carries increased risks of cardiovascular- and metabolic diseases in mothers and offspring during the life course. While the severe early-onset PE (EOPE) phenotype originates from impaired placentation in early pregnancy, late-onset PE (LOPE) is in particular associated with pre-existing maternal cardiovascular- and metabolic risk factors. We hypothesize that PE is associated with altered epigenetic programming of placental and fetal tissues and that these epigenetic changes might elucidate the increased cardiovascular- and metabolic disease susceptibility in PE offspring. Methods. A nested case-control study was conducted in The Rotterdam Periconceptional Cohort comprising 13 EOPE, 16 LOPE, and three control groups of 36 uncomplicated pregnancies, 27 normotensive fetal growth restricted (FGR) and 20 normotensive preterm birth (PTB) complicated pregnancies. Placental tissue, newborn umbilical cord blood leucocytes (UC-WBC) and umbilical vein endothelial cells (HUVEC) were collected and DNA methylation of cytosine-guanine dinucleotides was measured by the Illumina HumanMethylation450K BeadChip. An epigenome-wide analysis was performed by using multiple linear regression models. Results. Epigenome-wide tissue-specific analysis between EOPE and PTB controls revealed 5001 mostly hypermethylated differentially methylated positions (DMPs) in UC-WBC and 869 mostly hypomethylated DMPs in placental tissue, situated in or close to genes associated with cardiovascular-metabolic developmental pathways. Discussion. This study shows differential methylation in UC-WBC and placental tissue in EOPE as compared to PTB, identifying DMPs that are associated with cardiovascular system pathways. Future studies should examine these loci and pathways in more detail to elucidate the associations between prenatal PE exposure and the cardiovascular disease risk in offspring.
2017-09-06 | GSE103253 | GEO
Project description:Early onset preeclampsia (EOPE) in a model for early stage human placental trophoblast
| PRJNA488631 | ENA
Project description:Hypertension in pregnancy is the leading cause of morbidity and mortality in pregnancy, affecting up to 10% of all gestations1. Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, eclampsia and pre-eclampsia, all of which increase the risk of complications in both mothers and babies during gestation. Preeclampsia, in particular, is characterised by the new-onset of gestational hypertension in the presence of proteinuria or other organ damage. It affects 5-7% of pregnancies and causes approximately 76,000 maternal deaths and 500,000 foetal deaths worldwide each year2. The classification of preeclampsia has been evolving over the last decade. In 2013, American College of Obstetricians and Gynecologists (ACOG) and International Society for the Study of Hypertension in Pregnancy (ISSHP) in the absence of proteinuria included other symptoms/features including liver dysfunction, thrombocytopenia, cerebrovascular events or foetal growth restriction (FGR) in the diagnosis of preeclampsia 1,3,4. Despite the fact that preeclampsia is a multifactorial and heterogeneous disorder, it is now widely accepted that preeclampsia is stratified depending on the time of onset into: i) early-onset PE (EOPE) manifested before 34 weeks of gestation, and ii) late-onset PE (LOPE) manifested from 34 weeks of gestation. Although EOPE and LOPE share the same diagnostic criteria, these two phenotypes of preeclampsia lead to different outcomes. EOPE is commonly associated with FGR, abnormal uterine artery Doppler often leading to preterm birth and higher risk of post-pregnancy morbidities5,6. On the other hand, LOPE appears to be a less severe disorder, often with normal or slightly increased uterine resistance index and a low rate of FGR6,7. Distinct delineation between EOPE and LOPE is still not well understood, with most patients with preeclampsia presenting elements of both pathologies proposing a clinical spectrum for preeclampsia. The lack of untargeted discovery studies involving ‘omics’ analyses has impeded understanding of the molecular differences between these two phenotypes of preeclampsia. Notably, a study from 20058 utilised a proteomics approach using urine samples from a cohort of pregnant women with EOPE and healthy controls, however the differences between EOPE and LOPE were not elucidated. Another more recent bioinformatics study, identified overlapping pathogenic mechanisms between preeclampsia, hypertension and heart disease but could not stratify between EOPE and LOPE due to underreported of data related to individual phenotypes9. In this study, we conducted an unbiased, comprehensive proteomics investigation using plasma samples collected from patients with EOPE (n=17) and LOPE (n=11), compared with age- and BMI-matched normotensive controls (n=18). The use of plasma samples is able to better reflect the pathogenesis of EOPE and LOPE as systemic conditions centred by widespread endothelial dysfunction.
2023-03-11 | PXD026931 | Pride
Project description:Preeclampsia, a significant cause of maternal and perinatal morbidity and mortality, remains poorly understood in terms of its pathogenesis. This study aims to uncover novel and effective biomarkers for preeclampsia by conducting a comparative analysis of differential proteins in placentas from early-onset preeclampsia (EOPE) and normal pregnancies. Utilizing tandem mass tag (TMT)-based quantitative proteomics, we identified differentially expressed proteins in placental tissues from 15 EOPE patients and 15 normal pregnant women. These proteins were subsequently validated using parallel reaction monitoring (PRM). Our analysis revealed a total of 59 differentially expressed proteins, with 25 up-regulated and 34 down-regulated in EOPE placental tissues compared to those from normal pregnancies. Validation through PRM confirmed the differential expression of 6 proteins. Our findings suggest these 6 proteins could play crucial roles in the pathogenesis of EOPE, highlighting the potential involvement of the Estrogen signaling pathway and Dilated cardiomyopathy (DCM) pathway in the development of preeclampsia.
2024-08-20 | PXD055025 |
Project description:Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with significant maternal and fetal morbidity and mortality. Currently, there is a critical need for accurate, non-invasive biomarkers to facilitate early diagnosis and effective management of EOPE. In this study, we aimed to investigate the transcriptional alterations and non-invasive biomarker potential of peripheral blood microRNAs in patients with EOPE. Through our research, we successfully identified two reliable plasma miRNA biomarkers and proposed a circulating two-miRNA panel for the non-invasive early detection of EOPE. Additionally, we independently validated our findings in different patient cohorts using various technological platforms.
2023-06-14 | GSE234611 | GEO
Project description:For understanding the relationship of preeclampsia and placental methylation,we performed an epigenome-wide association study in a Chinese cohort containing 22 early-onset preeclampsia patients and 20 normal controls. We used Illumina Infinium HumanMethylation450k BeadChip for detecting the methylation level, and used placental genomic DNA as sample. most of the significant CpG sites were hypomethylated in EOPE in the Chinese cohort.
2019-06-30 | GSE125605 | GEO
Project description:In pregnancies involving preeclampsia (PE), there is evidence that the fetal-placental unit is under oxidative stress. Here we examined primary cell lines generated from umbilical cords (UC) delivered by mothers who had either a normal pregnancy or experienced early onset PE to determine whether the two had distinguishable phenotypes. While all UC provided outgrowths when established in 4 % O2, success was less assured for PE cords under ambient (20 % O2) conditions (P < 0.05). Moreover, proliferation rates of established PE lines, although similar to controls in 4 % O2, were significantly lower in 20 % O2. PE lines grown in 4 % O2 were also more susceptible to the pro-oxidant diethylmaleate than control lines, and unlike controls, were not protected by glutathione. Transcriptome profiling revealed only a few differentially regulated genes between PE lines and controls in 4 % O2 conditions, but confirmed the more severely stressed phenotype of the PE lines under 20 % O2. We conclude that the primary UC cell lines generated from PE births maintain a susceptibility to oxidative stress that is stable over many cell divisions, but whether the basis of this vulnerability is genetic or epigenetic remains unclear.
2014-08-31 | GSE54400 | GEO
Project description:H1 hESC were exposed to BMP4 (10 ng/ml) in absence of FGF2 for 0, 3, 12, 24, 72, and 120 h under both physiological (4 % O2) and atmospheric (20 % O2) conditions to identify candidate genes and gene networks associated with specification from totipotent precursor cells to trophoblast. RNA from cells under both conditions was isolated at each time point. Approximately 32,000 probe sets (out of 40,391) provided a signal above background at one of the time points. Of these, 14,478 showed a ≥2-fold (plus or minus) change (p<0.05) under 4 % O2, and 18,580 under 20 % O2. The data indicate the potential usefulness of hESC grown in presence of BMP4 and absence of FGF2 for studying both the emergence of trophoblast from hESC precursors and for its subsequent differentiation over time, space and varied O2 concentrations. Keywords: Genes and gene networks associated with specification from totipotent precursor cells to trophoblast
2009-05-10 | GSE10469 | GEO