Activated PRDM1-CREBBP Axis Contributes to Apoptosis and Impaired Invasion of Trophoblasts: A Novel Mechanism Underlying Preeclampsia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE255126 | GEO | 2025/01/08
REPOSITORIES: GEO
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Project description:Activated PRDM1-CREBBP Axis Contributes to Apoptosis and Impaired Invasion of Trophoblasts: A Novel Mechanism Underlying Preeclampsia
| PRJNA1073568 | ENA
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.
2018-09-12 | GSE119799 | GEO
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) is a pregnancy disorder characterized by high blood pressure and proteinuria that can cause adverse health effects in both mother and fetus. There is no current cure for PE other than delivery of the fetus. While the etiology is unknown, poor placentation of the placenta due to aberrant signaling of growth and angiogenic factors has been postulated as causal factors of PE. In addition, environmental contaminants, such as the metal cadmium (Cd), have been linked to placental toxicity and increased risk of developing PE. Here, we use a translational study design to investigate genomic and epigenomic alterations in both placentas and placental trophoblasts, focused on the angiogenesis-associated transforming growth factor-beta (TGF-β) pathway. Genes within the TGF-β pathway displayed increased expression in both the preeclamptic placenta and Cd-treated trophoblasts. In addition, miRNAs that target the TGF-β pathway were also significantly altered within the preeclamptic placenta and Cd-treated trophoblasts. Integrative analysis resulted in the identification of a subset of Cd-responsive miRNAs, including miR-26a and miR-155, common to preeclamptic placentas and Cd-treated trophoblasts. These miRNAs have previously been linked to PE and are predicted to regulate members of the TGF-β pathway. Results from this study provide future targets for PE treatment.
2016-07-12 | GSE84260 | GEO
Project description:To investigate the differentially expressed mRNAs and microRNAs in human placenta between early-onset preeclampsia (EO-PE) and preterm birth controls (PTB), next generation sequencing was performed in 5 paired EO-PE and PTB placentas.
2021-06-12 | GSE177049 | GEO
Project description: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.
2018-03-07 | GSE98224 | GEO
Project description:Preeclampsia (PE) is a heterogeneous disease which lacks pathophysiology-based subclassification. Current clinical classification is based on gestational age at diagnosis and severity of disease. However, PE placentas have heterogeneous findings on pathologic exam. We combined clinical, pathological, immunohistochemical (IHC), and transcriptomic profiling to better subclassify this disease. 303 PE and 1388 non-hypertensive controls were included, with subgroups of samples used for each analysis. Detailed clinical and placental pathologic data were abstracted from our Obstetric Registry. Tissue studio (Definiens) was used for IHC analysis. RNAseq was performed using Illumina-NovaSeq using our standard pipeline. We found that maternal vascular malperfusion (MVM) in the placenta is associated with preterm PE and small-for-gestation neonates, with further subclassification into groups with and without fetal vascular malperfusion (FVM). Interestingly, MVM with FVM was further characterized by loss of proliferative cytotrophoblast, as confirmed by p63 IHC. Finally, transcriptomic analysis identified pathways associated with hypoxia and reduced cell-proliferation in PE-MVM placentas, and further subclassified this group into syncytiotrophoblast (STB)hi and extravillous trophoblast (EVT)hi PE, confirmed by IHC for trophoblast lineage-specific markers. Our findings suggest that PE can be subclassified based on underlying pathophysiologic changes, allowing identification of pathways which can be targeted for diagnostic and therapeutic purposes.
2023-01-10 | GSE186257 | GEO
Project description:Preeclampsia (PE) is a hypertensive pregnancy disorder with increased risk of maternal and fetal morbidity and mortality. Abnormal extravillous trophoblast (EVT) development and function is considered to be the underlying cause of PE, but has not previously been modeled in vitro. We previously derived induced pluripotent stem cells (iPSC) from placentas of PE patients and characterized abnormalities in formation of syncytiotrophoblast and responses to changes in oxygen tension. In this study, we converted these primed iPSC to naïve iPSC, then derived trophoblast stem cells (TSC) and EVT to evaluate molecular mechanisms underlying PE. We found that primed (but not naïve) iPSC-derived PE-EVT have reduced surface HLA-G, blunted invasive capacity, and altered EVT-specific gene expression. These abnormalities correlated with promotor hypermethylation of genes associated with the epithelial-mesenchymal transition pathway, specifically in primed-iPSC derived PE-EVT. Our findings indicate that abnormal epigenetic regulation might play a role in the PE pathogenesis.
2024-03-27 | GSE243579 | GEO
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 ± 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 ± 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
Project description:During human pregnancy, a subset of placental cytotrophoblasts (CTBs) differentiates into cells that aggressively invade the uterus and its vasculature, anchoring the progeny and rerouting maternal blood to the placenta. In preeclampsia (PE), CTB invasion is limited, reducing placental perfusion and/or creating intermittent flow. This syndrome, affecting 4-8% of pregnancies, entails maternal vascular alterations (e.g., high blood pressure, proteinuria, and edema) ± fetal growth restriction. The only cure is removal of the faulty placenta, i.e., delivery. Previously we showed that defective CTB differentiation contributes to the placental component of PE, but the causes were unknown. Here, CTBs isolated from PE and control placentas were cultured for 48 h, enabling differentiation/invasion. In various severe forms of PE, transcriptomics revealed common aberrations in CTB gene expression immediately after isolation that resolved in culture. The upregulated genes included SEMA3B. Adding this protein to normal CTBs inhibited invasion and re-created aspects of the phenotype of these cells in PE. Additionally, SEMA3B downregulated VEGF signaling through the PI3K/AKT and GSK3 pathways, effects that were observed in PE CTBs. We propose that, in severe PE, the in vivo environment dysregulates CTB gene expression, the autocrine actions of the upregulated molecules, including SEMA3B, impair differentiation/invasion/signaling and patient-specific factors determine the signs.
2012-08-17 | GSE40182 | GEO