Effect of Prenatal Opioid Exposure on the Human Placental Methylome.
Effect of Prenatal Opioid Exposure on the Human Placental Methylome.
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DOI：
10.3390/biomedicines10051150
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发表时间：
2022-05-17
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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作者：
产前暴露于成瘾药物可导致胎盘表观遗传修饰，但尚未对产前阿片类药物暴露后胎盘DNA甲基化变化进行全甲基化评估。胎盘组织样本在分娩时从19个阿片类药物暴露和20个未暴露的对照足月妊娠中收集。使用Illumina Infinium HumanMethylationEPIC BeadChip分析胎盘DNA甲基化组。与阿片类药物暴露相关的差异甲基化CpG位点使用“limma”R包用线性模型鉴定。为了鉴定跨越多个CpG位点的差异甲基化区域（DMR），使用“DMRcate”R包。利用Enrichr软件对差异甲基化CpG位点和DMR定位的基因功能进行进一步注释。差异甲基化的CpG（n = 684，未校正的p < 0.005，和|∆β| ≥ 0.05）定位到258个基因（包括PLD 1、MGAM和ALCS 2）。差异甲基化区域（n = 199）位于174个基因（包括KCNMA1）。富集分析的顶部差异甲基化的CpG位点和区域表明，参与突触结构，化学突触传递和神经系统发育的基因的表观遗传调控被破坏。我们的研究结果表明，由于产前阿片类药物暴露引起的胎盘表观遗传变化可能导致胎盘功能障碍，导致胎儿脑发育异常和新生儿阿片类药物戒断症状。
Prenatal exposure to addictive drugs can lead to placental epigenetic modifications, but a methylome-wide evaluation of placental DNA methylation changes after prenatal opioid exposure has not yet been performed. Placental tissue samples were collected at delivery from 19 opioid-exposed and 20 unexposed control full-term pregnancies. Placental DNA methylomes were profiled using the Illumina Infinium HumanMethylationEPIC BeadChip. Differentially methylated CpG sites associated with opioid exposure were identified with a linear model using the ‘limma’ R package. To identify differentially methylated regions (DMRs) spanning multiple CpG sites, the ‘DMRcate’ R package was used. The functions of genes mapped by differentially methylated CpG sites and DMRs were further annotated using Enrichr. Differentially methylated CpGs (n = 684, unadjusted p < 0.005 and |∆β| ≥ 0.05) were mapped to 258 genes (including PLD1, MGAM, and ALCS2). Differentially methylated regions (n = 199) were located in 174 genes (including KCNMA1). Enrichment analysis of the top differentially methylated CpG sites and regions indicated disrupted epigenetic regulation of genes involved in synaptic structure, chemical synaptic transmission, and nervous system development. Our findings imply that placental epigenetic changes due to prenatal opioid exposure could result in placental dysfunction, leading to abnormal fetal brain development and the symptoms of opioid withdrawal in neonates.
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DOI：
10.1016/j.drugpo.2017.06.005
发表时间：
2017-08
期刊：
The International journal on drug policy
影响因子：
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