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电子废物拆解区产妇暴露重金属致新生儿 DNA 甲基化差异。

Differential DNA methylation in newborns with maternal exposure to heavy metals from an e-waste recycling area.

机构信息

Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, the Netherlands.

School of Environment, Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 511443, Guangdong, China.

出版信息

Environ Res. 2019 Apr;171:536-545. doi: 10.1016/j.envres.2019.01.007. Epub 2019 Jan 6.

Abstract

This study explored the effects of maternal exposure to e-waste environmental heavy metals on neonatal DNA methylation patterns. Neonatal umbilical cord blood (UCB) samples were collected from participants that resided in an e-waste recycling area, Guiyu and a nearby non-e-waste area, Haojiang in China. The concentrations of UCB lead (Pb), cadmium (Cd), manganese (Mn) and chromium (Cr) were measured by graphite furnace atomic absorption spectrometry. Epigenome-wide DNA methylation at 473, 844 CpG sites (CpGs) were assessed by Illumina 450 K BeadChip. The differential methylation of CpG sites from the microarray were further validated by bisulfite pyrosequencing. Bioinformatics analysis showed that 125 CpGs mapped to 79 genes were differential methylation in the e-waste exposed group with higher concentrations of heavy metals in neonatal UCB. These genes mainly involve in multiple biological processes including calcium ion binding, cell adhesion, embryonic morphogenesis, as well as in signaling pathways related to NFkB activation, adherens junction, TGF beta and apoptosis. Among them, BAI1 and CTNNA2 (involving in neuron differentiation and development) were further verified to be hyper- and hypo-methylated, respectively, which were associated with maternal Pb exposure. These results suggest that maternal exposure to e-waste environmental heavy metals (particularly lead) during pregnancy are associated with peripheral blood differential DNA methylation in newborns, specifically the genes involving in brain neuron development.

摘要

本研究探讨了母体暴露于电子废物环境重金属对新生儿 DNA 甲基化模式的影响。采集了来自中国 Guiyu 电子废物回收区和附近非电子废物区 Haojiang 的参与者的新生儿脐血 (UCB) 样本。通过石墨炉原子吸收光谱法测量 UCB 中铅 (Pb)、镉 (Cd)、锰 (Mn) 和铬 (Cr) 的浓度。通过 Illumina 450K BeadChip 评估 473,844 个 CpG 位点 (CpGs) 的全基因组 DNA 甲基化。通过亚硫酸氢盐焦磷酸测序进一步验证了微阵列中 CpG 位点的差异甲基化。生物信息学分析表明,在电子废物暴露组中,有 125 个 CpG 映射到 79 个基因发生了差异甲基化,这些基因主要涉及多个生物学过程,包括钙离子结合、细胞黏附、胚胎形态发生,以及与 NFkB 激活、黏着连接、TGF-β和细胞凋亡相关的信号通路。其中,BAI1 和 CTNNA2(涉及神经元分化和发育)分别被进一步验证为超甲基化和低甲基化,这与母体 Pb 暴露有关。这些结果表明,母体在怀孕期间暴露于电子废物环境重金属(特别是铅)与新生儿外周血的差异 DNA 甲基化有关,特别是涉及大脑神经元发育的基因。

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