Project name: Rattus norvegicus

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.Overall design: Dams were randomly distributed among two groups (3 dams per group) and exposed by caudal injection (0.3 ml/kg body weight) from GD 15 to PND 20 every 5 days (a total of 6 injections/dam). Dams of the control group received vehicle: ethanol 95%, Cremophor EL, and sterile water (1:1:8, v/v); dams of exposed group 1 received 0.002 mg/kg body weight (BW) of BDE-47 in vehicle, and dams of exposed group 2 received 0.2 mg/kg body weight (BW) of BDE-47 in vehicle. Dams and pups were kept together until weaning on PND 21. After weaning, dams, male and female pups were separated. One male and one female pup per litter were selected randomly and sacrificed by decapitation on PND 27. Total RNA was extracted from liver samples of these pups and used for microarray analysis.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Release date: 2010-01-13

Last updated: 2010-01-12