title: Epigenetic effects of low perinatal doses of flame retardant BDE-47 on mitochondrial and nuclear genes in rat offspring.
abstract: 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 0.2mg/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 0.2mg/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.
authors.affiliation: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: hmbyun@hsph.harvard.edu.
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.affiliation: Département Pédiatrie, Faculté de Médecine, Université de Sherbrooke, QC J1H 5N4, Canada. Electronic address: nora.meheni.benachour@USherbrooke.ca.
authors.forename: Nora
authors.initials: N
authors.lastname: Benachour
authors.affiliation: Institut National de la Recherche Agronomique, UMR1331, TOXALIM (Research Centre in Food Toxicology), Toulouse, France. Electronic address: dzalko@toulouse.inra.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zalko
authors.affiliation: Department of Statistics, University of Milano-Bicocca, Milan 20126, Italy; Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: m.frisardi@campus.unimib.it.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Frisardi
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: ecolicin@hsph.harvard.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.affiliation: Département Pédiatrie, Faculté de Médecine, Université de Sherbrooke, QC J1H 5N4, Canada. Electronic address: Larissa.Takser@USherbrooke.ca.
authors.forename: Larissa
authors.initials: L
authors.lastname: Takser
authors.affiliation: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA 02115, USA. Electronic address: abaccare@hsph.harvard.edu.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000367:Age Factors; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005260:Female; D005411:Flame Retardants / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D020071:Interspersed Repetitive Sequences / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar
chemical_list: D004272:DNA, Mitochondrial; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; C511295:2,2',4,4'-tetrabromodiphenyl ether
keywords: BDE-47; Brain; DNA methylation; Endocrine disruptors; Epigenetics; PBDE