Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA176597 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cultured Cyto and Syncytio-trophoblast samples exposed to varying degrees of hypoxia (expression)
| PRJNA176596 | ENA
Project description:Cultured Cyto and Syncytio-trophoblast samples exposed to varying degrees of hypoxia
| PRJNA176593 | ENA
Project description:Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.
2021-10-06 | MTBLS2148 | MetaboLights
Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast. RNA from cytotrophoblast from 2 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were run on the Illumina HT-12v4 Expression Array
2013-01-18 | E-GEOD-41331 | biostudies-arrayexpress
Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast. DNA from 2 cell types from 5 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were bisulfite converted and run on the Illumina HumanMethylation450 BeadChip
2013-01-18 | E-GEOD-41336 | biostudies-arrayexpress
Project description:Validation of an in vitro model of hypoxia using a primary cell culture of mouse embryonic fibroblasts (MEF) exposed to 1% oxygen at 37 degrees celsius. Control cells were exposed to atmospheric oxygen.
2014-03-01 | GSE54228 | GEO
Project description:Epithelial-mesenchymal transition in the differentiation of cyto- to extravillous trophoblast
| PRJNA298834 | ENA
Project description:We exposed three mouse strains to a high-fat high-carbohydrate diet, leading to varying degrees of metabolic syndrome. Comprehensive methylation and transcriptomic analysis found overlapping but also highly divergent changes in DNA methylation and gene expression, with pathway analysis suggesting a strategy for strain-specific targeted pharmacologic intervention of upstream regulators. Administeration of the drug GW4064 to target one of these genotype-dependent networks, the farnesoid X receptor pathway resulted in genotype-specific protection against dietary effects in BL6 as predicted by our epigenetic analysis.
2023-10-17 | GSE215954 | GEO
Project description:Previously we have shown that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were restricted by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450K array). The array identified 444 differentially methylated CpG loci in dNK-treated EVT compared to medium control (P<0.05). The represented genes from these loci had critical biological roles in cellular development, cellular organization and maintenance by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltranferase IV) were chosen for follow-up studies because of the biological relevance found in the research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced, and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by siRNA reduced trophoblast invasion, possibly through the altered MMP-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduce protein expressions. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility. This studied analyzed 17 samples of placental villous explant cultre exposed to different growth conditions. 6 Control samples (biological replicates) were cultured and unexposed to any other cells. 5 samples (biological replicates and from the same placentas as the controls) were cultured and exposed to conditions containing decidua natural killer cells trapped inside hollow fibres (thus only the factors secreted by the cells could interact with the explant culture and not the cells themselves. 6 samples (biological replicates and from the same placentas as the controls) were cultured and exposed to media containing IL-15. The DNA from the villous explants was isolated, bisulfite converted and run on the array.
2015-04-07 | E-GEOD-60885 | biostudies-arrayexpress
Project description:The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast.
2013-01-18 | GSE41336 | GEO