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Low-dose exposure to PBDE disrupts genomic integrity and innate immunity in mammary tissue

ABSTRACT: RNAseq results were generated from the normal mammary tissues of nude mice in a simple 2-group experiment (BDE-47 exposure vs. Vehicle-only exposure) after 16 weeks of exposure from subcutaneous osmotic minipumps

ORGANISM(S): Mus musculus

PROVIDER: GSE199054 | GEO | 2022/10/01

REPOSITORIES: GEO

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Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed Perinatally to 2,2',4,4'- Tetrabromodiphenyl Ether (BDE-47)

Project description:For the majority of lipophilic compounds adipose tissue is traditionally considered as storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposures may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) is a group of lipophilic flame retardants found in majority of human samples in North America. Their ability to alter physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using RNA-seq approach with subsequent bioinformatic analysis. Genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism were altered in expression in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.

2018-07-15 | GSE112207 | GEO

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via bulk RNA-sequencing

Project description:Similar to the scRNA-Seq data (GSE125272), a surgical menopausal (ovariectomized) mouse model was used to assess how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). The PBDE treatments include three analyzed flame retardants: BDE-47, BDE-100 and BDE-153. Bulk RNA-Seq data was created with treatment conditions lasting 1 week. Gene expression changes for PBDE treatment are relatively small compared to E2 treatment. However, along with other studies and experiments, this data is meant to contribute to greater understanding of the interaction of PBDE exposure and estrogen signaling.

2023-03-24 | GSE227872 | GEO

Whole brains and frontal lobes of rat offsprings exposed perinatally to low doses of 2,2',4,4'-tetrabromodiphenyl ether

Project description:Analysis of developmental toxicity of environmental toxin 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) at the level of gene expression. Dams of Wistar rats were exposed to environmentaly relevant doses of BDE-47 at gestation and lactation. Gene expression in total brains and frontal lobes was analysed in offspring on postnatal day 10.

2010-01-13 | GSE19867 | GEO

Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism

Project description:Purpose: The goal of this study was to investigate how PBDEs regulate both PCGs and lncRNAs in a PXR/CAR ligand-dependent and independent manner Methods: HepaRG cells, which are human-derived hepatic cells that accurately represent gene expression profiles of human liver tissue, were exposed to BDE-47 and BDE-99 at a dose of 25 μM for 24 hours. Differentially expressed lncRNA-PCG pairs were identified through DESeq2 and HOMER; significant canonical pathways were determined through Ingenuity Pathway Analysis (IPA). LncTar was used to predict the binding of 19 lncRNA-PCG pairs with known roles in drug-processing pathways. Results: Genome annotation revealed that the majority of the differentially expressed lncRNAs map to PCG introns. PBDEs regulated overlapping pathways with PXR and CAR such as protein ubiqutination pathway and peroxisome proliferator-activated receptor alpha-retinoid X receptor alpha (PPARα-RXRα) activation but also regulate distinctive pathways involved in intermediary metabolism. PBDEs uniquely down-regulated GDP-L-fucose biosynthesis, suggesting its role in modifying important pathways involved in intermediary metabolism such as carbohydrate and lipid metabolism. Conclusion: There is strong evidence that PBDEs regulate both PCGs and lncRNAs in a PXR/CAR ligand-dependent and independent manner

2020-01-08 | GSE143260 | GEO

BDE-47 CpG Methylomic Alterations in Human Embryonic Stem Cell-derived Neural Precursor Cells

Project description:Methylomic characterization of BDE-47 exposures in human neural precursor cells

2019-05-01 | GSE125465 | GEO

BDE-47 Transcriptomic Alterations in Human Embryonic Stem Cell-derived Neural Precursor Cells

Project description:Transcriptomic characterization of BDE-47 exposures in human neural precursor cells

2019-05-01 | GSE123458 | GEO

Liver of rat offsprings exposed perinatally to low doses of 2,2',4,4'-tetrabromodiphenyl ether

Project description:Background: Polybrominated diphenyl ethers are a group of flame-retardant chemicals appearing increasingly in the environment. Their health effects and mechanisms of toxicity are poorly understood.Objectives: We screened for the sensitive effects and mechanisms of toxicity of 2,2 ,4,4 -tetra-bromodiphenyl ether (BDE-47) by analyzing the gene expression profile in rats exposed to doses comparable to human exposure.Methods: Wistar dams were exposed to vehicle or BDE-47 (0.002 and 0.2 mg/kg body weight) every fifth day from gestation day 15 to postnatal day 20 by injections to caudal vein. Total RNA was extracted from the livers of pups and hybridized to the whole-genome RNA expression micro-arrays. The list of genes 2-fold differentially expressed was exported to PANTHER and Ingenuity Systems for analysis of enriched ontology groups and molecular pathways.Results: Oxidoreductase and transferase protein families were enriched in exposed rats as were these biological process categories: carbohydrate metabolism; electron transport; and lipid, fatty acid, and steroid metabolism. Four signaling pathways (cascades of activation of drug-metabolizing enzymes) and 10 metabolic pathways were significantly enriched. Drug-metabolizing enzymes appear to be regulated by BDE-47 through an aryl hydrocarbon receptorindependent mechanism. Direct interaction with retinoid X receptor or its upstream cascade may be involved. The main metabolic effects consisted of activation of metabolic pathways: alpha- and omega-oxidation of fatty acids, glycolysis, and starch hydrolysis.Conclusions: Altered expression of genes involved in metabolic and signaling pathways and functions of the organism occurs after perinatal exposure of rat offspring to BDE-47 at doses relevant for the general population.

2010-01-13 | GSE19868 | GEO

BDE-47 Transcriptomic Alterations in Human Primary Villous Cytrophoblasts

Project description:Transcriptomic characterization of BDE-47 exposed cultured primary human cytrophoblasts (2nd trimester) undergoing differentiation in vitro.

2018-09-01 | GSE104896 | GEO

Methylomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts

Project description:CpG methylomic characterization of BDE-47 exposed cultured primary human cytrophoblasts (2nd trimester) undergoing differentiation in vitro.

2018-09-01 | GSE115399 | GEO

Transcriptomic analysis of HepG2 cells treated with BDE-47, BDE-99, BDE-209 and their ternary mixture at 1nM as a dietary relevant concentration

Project description:Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals implied as flame re-tardants. Humans are mainly exposed to BDE-47, -99 and -209 congeners by diet. PBDEs are metabolic disruptors with liver as main target organ. To investigate their mode of action at a human relevant concentration, we exposed HepG2 cells to these congeners and their mixture at 1 nM for 72h, analyzing their transcriptomic and proteomic profiles. KEGG pathways and GSEA Hallmarks enrichment analyses evidenced that BDE-47 disrupted the glucose metabolism and Hypoxia pathway; all the congeners and the MIX affected lipid metabolism and signaling Hallmarks regulating metabolism as mTORC1 and PI3K/AKT/MTOR. These results were confirmed by glucose secretion depletion and increased lipid accumulation, especially in BDE-47 and -209 treated cells. These congeners also affected the EGFR/MAPK signaling; further, BDE-47 enriched the Estrogen pathway. Interestingly, BDE-209 and the MIX increased ERα gene expression, whereas all the congeners and the MIX induced ERβ and PPARγ. We also found that PBDEs modulated several lncRNAs and that HNRNAP1 represented a central hub in all the four interaction networks. Overall, despite the low concentration used, the PBDEs investigated affected glucose and lipid metabolism with different underlying modes of action, as highlighted by the integrated omics analysis. These results may support the mechanism-based risk assessment of these compounds in relation to liver metabolism disruption.

2022-10-28 | GSE216590 | GEO

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