Epigenetic effects of low perinatal doses of flame retardant BDE-47 on mitochondrial and nuclear genes in rat offspring.
Epigenetic effects of low perinatal doses of flame retardant BDE-47 on mitochondrial and nuclear genes in rat offspring.
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DOI：
10.1016/j.tox.2014.12.019
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发表时间：
2015-02-03
期刊：
影响因子：
4.5
通讯作者：
Baccarelli, Andrea A.
中科院分区：
文献类型：
--
作者：
Byun, Hyang-Min;Benachour, Nora;Zalko, Daniel;Frisardi, Maria Chiara;Colicino, Elena;Takser, Larissa;Baccarelli, Andrea A.
多溴联苯醚(PBDEs)是已知的干扰内分泌的化学物质，通常用作从电子产品到家具的各种阻燃剂。在发育早期接触多溴二苯醚与神经发育迟缓有关。尽管越来越多的证据表明，接触多溴二苯醚会对神经造成损害，但这些对大脑功能产生影响的分子机制仍不清楚。我们研究了围产期暴露于BDE-47对Wistar大鼠额叶表观遗传模式的影响。BDE-47是北美最活跃和最流行的BDE同系物。分别于妊娠第9天、第16天、出生后第1、8、15天灌胃0.002和0.2mgBDE-47。取出生后第41天仔鼠的额叶，测定线粒体细胞色素C氧化酶基因(mT-CO_1、mT-CO_2和mT-CO_3)的5-甲基胞嘧啶(5mC)、核基因组中与行为和脑功能相关的全核5-羟甲基胞嘧啶(5hmC)含量、重复元件L1Rn的5mC和核基因(BDNF、Crhr1、Mc2r、NR3c1和SNCA)的5mC。我们观察到mt-CO2的%5mC显著降低(与对照组的差值=−0.68%，p=0.010.2 mg/kg BDE-47)。重复元素L1Rn中的5 mC在0.002 mg/kgBDE-47剂量下降低(差值=−1.23%，p=0.02)。BDE-47染毒大鼠脑源性神经营养因子(BDNF)和神经营养因子(NR3C)核内5mC减少。然而，我们没有观察到多溴二苯醚毒性对大脑中大多数基因的DNA甲基化模式的显著影响。
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.
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