Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA328487 | ENA |
REPOSITORIES: ENA
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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:Preeclampsia is a disease of pregnant women, which is characterized by hypertension, proteinuria and chronic inflammation. There is a growing body of evidence that cause of preeclampsia lies within immunological aspect of pregnancy. This study aimed to analyze the role of CD74 in preeclampsia with a focus on its influence on communication between placental macrophages (Hofbauer cells) and trophoblasts. We have found CD74 to be highly dysregulated in preeclamptic placenta by real-time RT-PCR and Western blot methods. We identified Hofbauer cells to express the highest levels of CD74 in placenta by immunofluorescence and flow cytometry and that CD74 in preeclamptic Hofbauer cells is lower than in controls. We have performed a transcriptome analysis on human blood monocyte-derived macrophages that were non- or IL-4-activated and treated with small interfering RNA against CD74 (siRNA CD74) or non-targeting siRNA (siRNA non-targeting) as control.
2015-04-29 | E-MTAB-3309 | biostudies-arrayexpress
Project description:Prenatal development is a critical period for programming of neurological disease. Preeclampsia, a pregnancy complication involving oxidative stress in the placenta, has been associated with long-term health implications for the child, including an increased risk of developing schizophrenia and autism spectrum disorders in later life. We have shown previously, in a rodent model of placental oxidative stress, that culture medium conditioned by the placenta alters neuronal characteristics when applied to primary cortical cultures in vitro and mimics many of the neurodevelopmental changes observed in the offspring brain. To further investigate if molecules released by the placenta may be important mediators in foetal programming of the brain, we analysed if placental tissue delivered from patients with preeclampsia secreted molecules that could affect cortical cells in culture. Application of culture medium conditioned by preeclamptic placentae to mixed cortical cultures caused changes in neurons and astrocytes that were related to key changes observed in brains of patients with schizophrenia and autism, including effects on dendrite lengths, astrocyte number as well as glutamate and GABA receptors. Treatment of the placental explants with an antioxidant prevented neuronal abnormalities. Furthermore, we identified that bidirectional communication between neurons and astrocytes, potentially via glutamate, is required to produce the effects of preeclamptic placenta medium on cortical cells. Analysis of possible signalling molecules in the placenta conditioned medium showed that the secretion profile of extracellular microRNA, small posttranscriptional regulators, was altered in preeclampsia and partially rescued by antioxidant treatment of the placental explants. Predicted targets of these differentially abundant microRNAs were linked to neurodevelopment and the placenta. The presented study provides further evidence that the diseased placenta may release factors that damage cortical cells in the brain and suggests the possibility of targeted antioxidant treatment of the placenta to prevent neurodevelopmental disorders.
2019-02-11 | GSE110786 | GEO
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
Project description:Epigenome analysis of normal and preeclamptic placenta samples
| PRJNA248043 | ENA
Project description:The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n=60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases. 23 preeclamptic, and 37 control placentas included in this study were collected during the years of 2004-2008 and hybridized in two batches to microarrays. Samples were randomized across arrays to control for array and batch variability.
2010-12-10 | E-GEOD-25906 | biostudies-arrayexpress
Project description:Epigenetics and Preeclampsia: Defining Functional Epimutations in the Preeclamptic Placenta Related to the TGF-β Pathway [methylation]
| PRJNA296823 | ENA
Project description:Purpose: The goals of this study is to compare and profile the smallRNA transcriptome of the placenta in preeclamptic and normal patients using RNA sequencing. Methods: Placental and Placental vesicles (STB-EVs) smallRNA profiles of normal and preeclamptic patients were generated by deep sequencing using Illumina HISEQ. FASTq.gz files were compressed with OASIS compressor and alignment was done with OASIS 2.0 ( by trimmimng with trimmomatic, aligning using default OASIS 2.0 aligning papameters). Quantitative PCR validation was performed using TaqMan gene expression assays Results: This contains a set of three parallel smallRNA sequencing experiments involving placenta tissue, medium/large STB-EVs and small STB-EVs. Comparison between PE and normal pregnancy placental tissue revealed 134 (p-value of <0.05 ) while in medium/large STB-EVs, 101 and in small STB-EVs, 16 (adjusted P-value of <0.05) differentially expressed small RNA We identified a number of mechanistic and biomarker targets, which were validated with qRT–PCR and confirmed to be signifficantly DE. The differentially expressed analysis identified potential yet undescribed small RNAs that may contribute to the pathogenesis of preeclampsia or/and may act as biomarkers of the disease. Conclusions: Our study represents the first combined analysis of placenta, medium/large and small STB-EV transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results identified potential Placenta EV small RNA biomarkers that can help diagnose the preeclampsia
2021-12-17 | GSE190972 | GEO
Project description:Preeclampsia (PE) is a major contributor of maternal mortality with uncertain etiology. Recent studies suggested that epigenetic modifications, including DNA methylation, play a vital role in the development of PE. In this study, we have mapped genome-wide distribution of 5-methylcytosin (5-mC) and 5-hydroxymethylcytosine (5-hmC) using MeDIP and (h)MeDIP in the placentas from severely preeclamptic patients and normal controls. A total 194485 pooled 5-mC peaks and 138133 pooled 5-hmC peaks were identified, of which 714 5-mC peaks and 119 5-hmC peaks showed significant difference between patients and controls (>2-fold, p<0.05).To our knowledge, this is the first report of DHMRs (Differentially Hydroxy-Methylated Regions) in preeclamptic placenta. We not only confirmed the aberrant DNA methylated regions in the process of preeclampsia reported previously, but also identified unreported regions. A total of 4 selected DMRs (Differentially Methylated Regions) were also confirmed by MassARRAY EppiTYPER. Of these, PTPRN2, which had low level of 5-mC and high level of 5-hmC at gene body, was further verified to have lower methylation level at promoter regions in case group compared with controls. In conclusion, our study provided genome-wide distribution of 5-mC and 5-hmC in severe PE and normal controls, which have further clinical value for the identification of diagnostic and therapeutic markers for severe PE. Examination of 5-mC and 5-hmC pattern in 4 control cases' tissue and 4 severely Preeclamptic Placentas cases' tissue.
2014-12-13 | E-GEOD-63743 | biostudies-arrayexpress