DNA methylation in Early Onset Preeclamptic placentas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE44667 | GEO | 2013/06/21
SECONDARY ACCESSION(S): PRJNA191068
REPOSITORIES: GEO
Similar Datasets
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. Bisulfite converted DNA from 20 third trimester early onset preeclampsia placentas and 20 gestational age matched controls
2013-06-21 | E-GEOD-44667 | biostudies-arrayexpress
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
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.
2013-06-21 | GSE44711 | GEO
Project description:VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p<2.7x10-8), PICALM-V1aR (p<0.006), and OT-R-V1aR (p<0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.
2024-05-22 | PXD050049 | Pride
Project description:The maternal signs of preeclampsia, principally the new onset of high blood pressure, are thought to occur secondary to faulty placentation. Previous studies profiled the gene expression patterns of chorionic villi, the maternal-fetal interface or isolated cytotrophoblasts in this pregnancy complication. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would give us new insights into the role of these cells in preeclampsia pathogenesis.
2017-01-24 | GSE93839 | GEO
Project description:Background Mutations in STOX1 were proposed as causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation. Methodology and Principal Findings In the present study, we have developed a choriocarcinoma cell line overexpressing STOX1. This overexpression results in the transcriptional modification of 12.5% of the genes, some of them being direct targets as shown by chromatin immunoprecipitation. STOX1 overexpression correlates strongly and specifically with transcriptomic alterations in preeclamptic placentas (r=0.30, p=9.10-7). Numerous known key modulators of preeclampsia (such as Endoglin, Syncytin, human chrionic gonadotrophin-hCG-, and Glial Cell Missing Homolog -GCM1-) were modified in these transformed choriocarcinoma cells. Conclusions Our results contribute to reconcile contradictory data about the involvement of STOX1 in preeclampsia. In addition, they strongly suggest that anomalies in STOX1 expression are associated with the onset of preeclampsia, thus indicating that this gene should be the target of future studies. Furthermore, our cellular model could constitute an invaluable resource for studying specific aspects of this human disease.
2008-11-07 | GSE13475 | GEO
Project description:Acute chorioamnionitis (aCA) is a commonly reported histologic lesion in at least 40% of spontaneous preterm deliveries. It is typically characterized by an infiltration of maternal neutrophils into the chorioamniotic membranes and is also associated with other placental inflammatory lesions such as acute intervillositis and acute villitis. DNA methylation (DNam) is an easily measurable epigenetic mark, which is more stable than mRNA. While DNAm may influence gene expression in specific cell types, it may also reflect altered cell composition. Studies have previously documented aCA-associated cellular changes primarily in the context of a polymicrobial invasion of the amniotic space. We, thus hypothesize that changes in DNAm associated with aCA will occur predominantly as a consequence of the response to infection, in particular due to alterations in the number of neutrophils and/or other alterations in cell populations inherent to the placenta. Pooled chorionic villus samples (22 aCA cases, 22 non-aCA cases) and fetal membranes (amnion and chorion) (9 aCA cases, 7 non-aCA cases) were evaluated using the Illumina EPIC array, which quantifies DNAm at >850,000 sites in the genome. We identified 66 differentially methylated sites associated with aCA (FDR <0.15, methylation difference >0.05). At the same thresholds, ~20% chorionic villi sites were also differentially methylated in chorion, but none were observed in amnion. Using publicly available datasets, we identified 2069 neutrophil-specific CpGs by differential methylation analysis. Euclidean clustering of our chorionic villi DNAm data (n=44 samples) using 2069 neutrophil-specific CpG sites largely separated aCA cases from the non-aCA cases, suggesting activation of innate immune responses in aCA-associated placentas.
2018-11-06 | GSE115508 | 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
Project description:Background; Mutations in STOX1 were proposed as causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10% of human pregnancies. However, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation. Methodology and Principal Findings; In the present study, we have developed a choriocarcinoma cell line overexpressing STOX1. This overexpression results in the transcriptional modification of 12.5% of the genes, some of them being direct targets as shown by chromatin immunoprecipitation. STOX1 overexpression correlates strongly and specifically with transcriptomic alterations in preeclamptic placentas (r=0.30, p=9.10-7). Numerous known key modulators of preeclampsia (such as Endoglin, Syncytin, human chrionic gonadotrophin-hCG-, and Glial Cell Missing Homolog -GCM1-) were modified in these transformed choriocarcinoma cells. Conclusions; Our results contribute to reconcile contradictory data about the involvement of STOX1 in preeclampsia. In addition, they strongly suggest that anomalies in STOX1 expression are associated with the onset of preeclampsia, thus indicating that this gene should be the target of future studies. Furthermore, our cellular model could constitute an invaluable resource for studying specific aspects of this human disease. Experiment Overall Design: Microarrays expression
2008-11-14 | E-GEOD-13475 | biostudies-arrayexpress
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.
2014-12-13 | GSE63743 | GEO