Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and vascular function in rat placentas

ABSTRACT: Preeclampsia (PE) is a hypertensive disorder and a leading cause of maternal and fetal mortality and morbidity during human pregnancy. Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates vascular development and function during pregnancy. Here, we report the important role of endogenous AhR ligands in vascular growth and function during pregnancy using a rat model. We found that exposure of pregnant rats to an endogenous AhR ligand (ITE, [2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester]) elevated maternal blood pressure and induced proteinuria, while decreased uteroplacental blood flow and fetal/ placental growth, all of which are hallmarks of PE. ITE also dysregulated transcriptomic profiles of rat placentas in a fetal sex-specific manner. The ITE-dysregulated genes were enriched in biological function and pathways highly relevant to diseases of heart, liver, and kidney, vascular function, and inflammation responses. Collectively, we conclude that dysregulation of endogenous AhR ligands may contribute to the PE-impaired vascular function through fetal sex-specific regulation of immune cell infiltration and transcriptomes. These AhR ligand-activated genes and pathways might represent promising therapeutic and sex-specific targets for PE-impaired vascular function.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE250269 | GEO | 2025/02/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE250269_RSEM.RatPla.txt.gz	Txt

Items per page:

1 - 2 of 2

Similar Datasets

Endogenous aryl hydrocarbon receptor ligands-dysregulated transcriptomic profiles and endothelial function in human fetal endothelial cells

Project description:Preeclampsia (PE) is a hypertensive disorder and a leading cause of maternal and fetal mortality and morbidity during human pregnancy. Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, regulates vascular development and function during pregnancy. Here, we report the important role of endogenous AhR ligands in endothelial growth and function during pregnancy using human umbilical vein endothelial cells (HUVECs) as a model. We found that ITE, ([2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester], an endogenous AhR ligand) decreased cell proliferation and monolayer integrity in HUVECs in vitro. ITE also dysregulated transcriptomic profiles of HUVECs in a fetal sex-specific manner. The ITE-dysregulated genes were enriched in biological function and pathways highly relevant to cardiovascular diseases, vascular function, and inflammation responses. We conclude that dysregulation of endogenous AhR ligands may contribute to the PE-impaired endothelial function through fetal sex-specific regulation of endothelial transcriptomes. These AhR ligand-activated genes and pathways might represent promising therapeutic and sex-specific targets for PE-impaired endothelial function.

2025-02-10 | GSE250196 | GEO

Expression profiling of four replicates of MCF-7 cells treated with 100nM TCDD

Project description:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds pollutants, therapeutic drugs and endogenous ligands. The AHR is expressed in all breast cancer subtypes and it can switch the aggressiveness of breast cancer cells from low to high depending on the ligand that it binds. Jagged 1 (JAG1) is a NOTCH receptor ligand that is overexpressed in basal-like breast cancer. JAG1 promotes breast cancer progression in part by increasing the migratory and invasive activity of breast cancer cells (BCCs). The regulation of JAG1 by AHR in MCF-7 and MDA-MB-231 BCCs by two AHR ligands (TCDD and ITE) was investigated in this report. TCDD is the prototype AHR ligand, and ITE is a non-toxic endogenous AHR ligand with anti-cancer activity. Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and cell movement. Short interfering RNA (siRNA)-directed knockdown of AHR confirmed TCDD-stimulated decreases in JAG1 required AHR expression. TCDD-induced reductions in JAG1 were inhibited by the AHR antagonist CH-223191. The endogenous non-toxic AHR ligand ITE also reduced JAG1 by activating AHR in BCCs. MDA-MB-231 are basal-like BCCs that are highly migratory and invasive, and these cancer cell attributes were significantly inhibited by ITE. We reduced JAG1 with targeting siRNA, and the outcome mirrored ITE, it suppressed TNBC cell migration and invasive activity. Collectively, these findings are the first showing that ITE is a tumor-suppressing AHR ligand in TNBC cells in part because it reduces JAG1 expression

2018-08-15 | GSE98514 | GEO

Activation of AhR by ITE in DCs induces differential gene expression over time.

Project description:To evaluate the effects of AhR activation in dendritic cells (DCs) over time, DCs isolated from human blood or murine spleens were incubated with the AhR ligand ITE for 6 hours, 18 hours, or 72 hours. Treatment with ITE was found to induce transcriptional programs associated with immunoregulatory/ immunosuppressive mchanisms.

2021-08-04 | GSE155712 | GEO

Sexual Dimorphism of Preeclampsia-Dysregulated Transcriptomic Profiles and Endothelial Function in Fetal Endothelial Cells

Project description:Preeclampsia-offspring have increased risks of developing cardiovascular disorders in adulthood, implicating that preeclampsia programs fetal vasculature in utero. Fetal sex is associated with the risk of preeclampsia but the underlying mechanisms are unclear. We hypothesize that preeclampsia alters fetal endothelial gene expression and disturbs cytokines and growth factors-induced endothelial function in a fetal sex-specific manner. Methods: RNAseq analysis was performed with female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive and preeclamptic (PE) pregnancies and verified by RT-qPCR. Results: PE dysregulate 926 and 172 genes in female and male P0-HUVECs, respectively. PE differentially dysregulates cardiovascular diseases (i.e. heart failure) and endothelial function (i.e. endothelial cell migration, calcium, eNOS, and iNOS signaling)-associated genes in female and male P0-HUVECs. PE also differentially dysregulates TNF-, TGFβ1-, FGF2-, and VEGFA-regulated gene networks in female and male P0-HUVECs. Conclusions: There are sexual dimorphisms of PE-dysregulated cardiovascular diseases and endothelial function-associated genes/pathways in fetal endothelial cells in association with sexual dimorphisms of PE-dysregulated fetal endothelial function.

2019-07-02 | GSE116428 | GEO

Sex-dependent Effects of AHR Activation in Endothelial Cells in Hypoxic Conditions

Project description:Chronic kidney disease (CKD) is a risk factor for peripheral arterial disease, however the molecular mechanisms linking the pathobiologies are ill-defined. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, has been previously shown to regulate angiogenesis. Notably, CKD results in the accumulation of metabolites that are endogenous ligands for the AHR. Results from animal work showed in male mice with CKD, AHRecKO lead to improvements in limb perfusion without improvements in muscle contractile or mitochondrial function. There was no effect of genotype observed in female mice. To assess these sex-dependent effects we cultured hypoxic endothelial cells from male and female mice and found inherent sex differences in AHR activating potential. Further to this, we performed bulk RNA sequencing and identified several angiogenic genes that were differentially expressed. In summaryn mice with CKD, endothelium-specific deletion of the AHR improved blood perfusion in muscle but did not confer improvement in mitochondrial function or muscle strength. Interestingly, these changes were observed in male, but not female, mice. Cell culture experiments revealed inherent sex-differences in gene expression.

2024-02-14 | GSE234508 | GEO

Cryo-EM structure of the cytosol AhR complex

Project description:Aryl hydrocarbon receptor (AhR) is an important ligand-activated transcription factor involved in the regulation of various important physiological functions. AhR can be activated by a variety of signals with different affinities, including xenobiotics and endogenous signals. In the absence of ligand, AhR forms a stable multiprotein complex in the cytosol with the chaperone Hsp90 and co-chaperon p23, XAP2.

2022-12-26 | PXD038120 | JPOST Repository

Sexually dimorphic crosstalk at the maternal-fetal interface

Project description:The first trimester is a critical window of maternal-fetal communication for pregnancy. Using single cell RNA-sequencing to dissect placenta heterogeneity, we identified five major cell types (trophoblasts, stromal cells, hofbauer cells, antigen presenting cells and endothelial cells). We identified seven unique trophoblast subclusters, including new subtypes that transition into the terminal cell types, extra-villous trophoblasts and syncytiotrophoblasts. As fetal sex impacts pregnancy, we analyzed sex differences in each cell type and identified differences in immune cell function. TGFβ1, β-estradiol, and dihydrotestosterone emerge as upstream regulators of sexually dimorphic genes in a cell type specific manner. Thus, the fetal contribution at the maternal-fetal interface is cell and sex specific.

2020-08-20 | GSE131696 | GEO

Dual specificity phosphate 1 (DUSP1) has a key non-invasive predictive marker in preeclampsia

Project description:Preeclampsia (PE) is a multisystem pregnancy complication constituting a major cause of maternal and fetal morbidity and mortality. Factors pointing to a placental origin are the development of the pathology only during pregnancy, and its disappearance in the post-partum period. Our study identified a specific signature of PE including five Gene Ontology clusters including "angiogenesis and differentiation", "cell cycle”, "cell adhesion", "inflammatory response" and "cellular metabolism". Interestingly, we identified DUSP1 as a biomarker of interest in PE. Pregnant women with PE have a higher concentration of DUSP1 in serum in the first trimester of pregnancy compared to healthy donors. Interesting, at a distance from childbirth DUSP1 finds a rate like the control group showing the predictive interest of DUSP1 as a predictive biomarker of PE

2024-03-26 | GSE262147 | GEO

Preliminary Interpretations of Epigenetic Profiling of Cord Blood in Preeclampsia

Project description:Preeclampsia (PE) is characterized by new-onset hypertension after 20 weeks of pregnancy and results in high maternal and fetal mortality worldwide. It has been reported that PE is associated with abnormalities in the umbilical cord and cord blood. However, previous studies were focused primarily on the transcriptomics level, while the underlying gene regulatory landscapes are still unclear. Thus, we performed the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) using the umbilical cord blood samples collected from a patient with superimposed PE and three healthy donors to uncover the chromatin accessibility changes attributed to PE. We have identified genes associated with immunomodulation and hypoxia response that have higher chromatin accessibility close to their transcription start sites. Motif analysis indicated that the GATA family transcription factor binding was enriched in PE and may play an essential regulatory role in the disease progression. Overall, our findings provide an overview of gene regulatory programs and the corresponding downstream pathways associated with PE that may influence the placenta function and fetal growth.

2022-06-03 | GSE199479 | GEO

Analysis of retroviral MLT1 enhancer-driven genes identifies over-expression of EPS8L1 as an early-stage initiator of both oxidative stress and poor trophoblast invasiveness in the pregnancy disorder preeclampsia

Project description:In the human-specific disorder of pregnancy preeclampsia (PE) we find dysregulation of multiple genes associated with the cis-regulatory elements (CREs) derived from mammalian-specific endogenous retrovirus (ERV3-MLT1)

2024-04-08 | GSE263305 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data