Developmental Exposure to 2,2’,4,4’-Tetrabromodiphenyl Ether Permanently Alters Blood-Liver Balance of Lipids in Male Mice
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PROVIDER: PRJNA473916 | ENA |
REPOSITORIES: ENA
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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
Project description:Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives starting 1965 and were recently withdrawn from commerce in North America and Europe. Approximately 1/5 of the total U.S. population were born when environmental concentrations of PBDE plateaued at their maximum. Accumulating evidence suggests that developmental exposures to PBDE may result in long-lasting programming of liver metabolism. In this study, CD-1 mice were exposed prenatally or neonatally to 1 mg/kg body weight of 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47), and changes in liver gene histology, transcriptome, and liver-blood balance of triglycerides were analyzed in 10 month old male offspring. In both exposure groups, long-term reprogramming of lipid metabolism was observed, including increased liver triglycerides and decreased blood triglycerides, and altered expression of metabolic genes in the liver. Significant upregulation of lipid influx transporter Cd36 2.3- and 5.7-fold in pre- and neonatal exposure groups respectively was identified as a potential mechanism of blood/liver imbalance of triglycerides. Analysis of our and previously published all-genome gene expression data identified changes in expression of ribosomal protein genes as a transcriptomic signature of PBDE exposure. Further comparison of our new data and published data demonstrate that low doses (0.2 mg/kg body weight) of PBDE induce long-lasting up-regulation of ribosomal genes, suppression of Cd36 in liver and increase circulating triglycerides in blood, while moderated doses (≥ 1 mg/kg body weight) produce opposite long-lasting effects. To conclude, this study shows that an environmentally relevant developmental exposures to BDE-47 permanently alter lipid uptake and accumulation in the liver, with low and moderate doses having opposite effect on liver transcriptomics and triglyceride balance. Similar effects of pre- and neonatal exposures point at hepatocyte maturation as a sensitive window of the liver metabolism programming. These results suggest that PBDE exposure may be an important factor increasing risks of cardio-vascular disease and non-alcoholic fatty liver disease. The translational relevance of these findings for human remain to be studied.
2019-07-19 | GSE115143 | GEO
Project description:Toxicity of PBDE for male reproductive system was shown in several human and animal studies, however long lasting effects of perinatal exposures on male reproduction are yet poorly understood. In this study pregnant Wistar rats were exposed to 0.2 mg/kg 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) from gestation day 8 till postnatal day 21 and testis transcriptome was analyzed on postnatal day 120 in offspring. Exposed animals had significant change in testes transcriptome including suppression of genes essential for spermatogenesis and activation of immune response genes. In particular exposed animals had on average 4 fold decreased expression of protamine and transition protein genes in testes suggesting that histone-protamine exchange may be dysregulated in the course of spermatogenesis resulting in exposure legacy transfer to the next generation via aberrant sperm epigenome.
2019-08-10 | GSE85420 | GEO
Project description:To develop molecular indicators of neurodevelopmental disorders related to the exposure to external chemicals, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to influence neuronal differentiation from embryonic stem cells. Thalidomide (TMD), bisphenol A (BPA), 4-hydroxy-2,2',3,4',5,5',6-heptachlorobiphenyl (4OH-PCB187) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) were exposed to human embryonic stem (ES) cell-derived sphere on day 3 after starting sphere formation for 72 hours. Gene expression analysis on the stage of sphere development showed chemical specific characteristics.
2020-05-28 | GSE151239 | GEO
Project description:Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives in a wide range of polymers starting in 1965 and were recently withdrawn from commerce in North America and Europe. Generations that were exposed perinatally to the highest environmental doses of PBDE have now reached 5-20 years of age and in the U.S. account for 1/5 of the total population. Emerging data indicates long-term impairment of metabolic health by PBDE exposure in humans and laboratory animals. We hypothesize that exposure to PBDE during sensitive developmental windows may result in long-lasting changes in liver metabolism. In this study pregnant CD-1 mice were exposed to 0.2 mg/kg 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47) from gestation day 8 till postnatal day 21 and liver RNA-seq was performed on the last day of dam exposure and on postnatal week 20 in male offspring. Several groups of metabolic genes, including ribosomal and mitochondrial genes were significantly upregulated at both time-points. Genes regulated via mechanistic target of rapamycin (mTOR pathway), the gatekeeper of metabolic homeostasis, were whether up- or down- regulated at both time-points. Thus, perinatal exposure to environmentally relevant doses of BDE-47 in laboratory mice results in long-lasting changes in liver metabolism. Our evidence suggests involvement of the mTOR pathway in the observed metabolic programming of liver.
2018-02-22 | GSE85221 | GEO
Project description:Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed Perinatally to 2,2',4,4'- Tetrabromodiphenyl Ether (BDE-47)
| PRJNA445270 | ENA
Project description:This study was conducted to identify the genes involved in the synthesis of membrane-spanning ether lipids in Thermotoga maritima MSB8.
2022-10-26 | GSE211547 | GEO
Project description:RNA-seq provided a general overview of the gene expression profiles of the digestive glands of Mactra veneriformis exposed to 2, 2′,4,4′-tetrabromodiphenyl ether (BDE-47, a type of widely used brominated flame retardants).
2019-10-19 | GSE88918 | GEO
Project description:This study was conducted to identify the proteins involved in the synthesis of membrane-spanning ether lipids in Thermotoga maritima.
2023-10-03 | PXD035794 | Pride
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