期刊
TOXICOLOGY
卷 328, 期 -, 页码 152-159出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2014.12.019
关键词
BDE-47; PBDE; Endocrine disruptors; Epigenetics; DNA methylation; Brain
资金
- ANSES (Agence nationale de securite sanitaire de l'alimentation, de l'environnement et du travail, France) [EST-08-46]
- FRQ-S
- CIHR (the Canadian Institutes of Health Research)
- FRQS (Fonds de Recherche du Quebec - Sante)
- United States National Institute of Environmental Health Sciences [R21ES022694, ES021357, ES021733]
Polybrominated diphenyl ethers (PBDEs) are known endocrine disrupting chemicals used commonly as flame retardants in everything from electronics to furniture. Exposure to PBDEs during early development has been linked to neurodevelopmental delays. Despite mounting evidence of neurological harm from PBDE exposure, the molecular mechanisms underlying these effects on brain function remain unknown. We examined the effects of perinatal exposure to BDE-47, the most biologically active and prevalent BDE congener in North America, on epigenetic patterns in the frontal lobe of Wistar rats. Dams were gavaged with BDE-47 (0.002 and 0.2 mg/kg body weight) at gestation days 9 and 16, and postnatal days 1, 8, and 15. Frontal lobes from offspring at postnatal day 41 were collected to measure 5-methylcytosine (5mC) in mitochondrial cytochrome c oxidase genes (Mt-co1,Mt-co2, and Mt-co3), global nuclear 5-hydroxymethylcytosine (5hmC) content, 5mC in repetitive elements L1Rn, and 5mC in nuclear genes (Bdnf, Crhr1, Mc2r, Nr3c1, and Snca) related to behavioral and brain functions in the nuclear genome. We observed a significant decrease in %5mC in Mt-co2 (difference from control=-0.68%, p=0.01 at the 0.2 mg/kg BDE-47). 5mC in repetitive elements L1Rn decreased at 0.002 mg/kg BDE-47 (difference=-1.23%, p=0.02). Decreased nuclear 5mC was observed in Bdnf and Nr3c1 in BDE-47 exposed rats. However, we did not observe significant effects of PBDE toxicity on DNA methylation patterns for the majority of genes in the brain. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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