Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA 02115, USA.
Département Pédiatrie, Faculté de Médecine, Université de Sherbrooke, QC J1H 5N4, Canada.
Toxicology. 2015 Feb 3;328:152-9. doi: 10.1016/j.tox.2014.12.019. Epub 2014 Dec 19.
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.
多溴联苯醚（PBDEs）是一种已知的内分泌干扰化学物质，常用于电子设备到家具等各种产品中作为阻燃剂。在早期发育过程中接触 PBDEs 与神经发育迟缓有关。尽管越来越多的证据表明 PBDE 暴露会对神经系统造成伤害，但这些对大脑功能影响的分子机制仍不清楚。我们研究了围产期暴露于 BDE-47（北美最具生物活性和最普遍的 BDE 同系物）对 Wistar 大鼠额叶表观遗传模式的影响。在妊娠第 9 天和第 16 天以及产后第 1、8 和 15 天，通过灌胃给予母体 BDE-47（0.002 和 0.2mg/kg 体重）。在产后第 41 天收集后代的额叶组织，以测量线粒体细胞色素 c 氧化酶基因（Mt-co1、Mt-co2 和 Mt-co3）中的 5-甲基胞嘧啶（5mC）、核内 5-羟甲基胞嘧啶（5hmC）含量、重复元件 L1Rn 中的 5mC 以及核基因（Bdnf、Crhr1、Mc2r、Nr3c1 和 Snca）中的 5mC，这些基因与核基因组中的行为和大脑功能有关。我们观察到 Mt-co2 中的 5mC 显著减少（与对照组相比，0.2mg/kg BDE-47 组的差异为-0.68%，p=0.01）。0.002mg/kg BDE-47 时重复元件 L1Rn 中的 5mC 减少（差异=-1.23%，p=0.02）。暴露于 BDE-47 的大鼠的 Bdnf 和 Nr3c1 中观察到核内 5mC 减少。然而，我们没有观察到 PBDE 毒性对大脑中大多数基因的 DNA 甲基化模式产生显著影响。
