基于胎盘基因表达谱研究孕期烟草暴露对孕妇和胎儿的影响

Effects of tobacco exposure during pregnancy on pregnant women and foetuses based on placental gene expression profiling

目的扩展孕期烟草暴露对孕妇和胎儿造成影响的分子机制的认识。方法首先系统检索NCBI GEO和EBI ArrayExpress数据库,挑选符合条件的吸烟和不吸烟2组孕妇胎盘组织的基因表达谱数据集。然后整合并校正了数据集间的差异,采用差异表达、功能注释、富集分析、回归分析等多种生物信息方法和模型研究烟草暴露对孕妇和胎儿的影响。结果通过合并后的表达谱数据找到476条差异表达的基因(FDR<0.5,|log_(2)FC|>0.3),其中上调的基因317条,下调的基因159条。随后通过KEGG、GO以及Reactome、MSigDb对显著差异表达的基因进行功能注释和富集分析,发现这些基因主要出现在细胞外结构组织(P=1.10×10^(-28))、细胞外基质组织(P=3.44×10^(-25))以及间充质发育(P=2.60×10^(-13))等通路上。进一步针对烟草暴露标志物研究,采用回归分析发现CDCA7L基因在校正了母亲年龄等混杂因素后,与母亲血清中的可的宁含量最相关(FDR=0.046)。结论通过系统研究,探讨了孕妇和胎儿在烟草暴露环境中可能受到影响的通路,烟草暴露影响胎盘功能和胎儿生长的机制,对后续深入的分子机制研究提出思路。

Objective To expand the understanding of the molecular mechanisms underlying tobacco exposure during pregnancy on pregnant women and their foetuses.Methods Firstly,the NCBI GEO database and EBI ArrayExpress database were systematically searched,and two gene expression profile datasets from placental tissues of smoking and non-smoking pregnant women were selected.After integrating and correcting these datasets,various bioinformatics methods and models including differential expression,functional annotation,enrichment analysis and regression analysis were applied to study the effects of tobacco exposure on pregnant women and foetuses.Results Amongst 476 significantly differentially expressed genes(FDR<0.5,|log 2FC|>0.3),317 were up-regulated and 159 were down-regulated.After functional annotations and enrichment analyses using KEGG,GO,Reactome and MSigDb,these genes mainly appeared in extracellular structure(P=1.10×10^(-28)),extracellular matrix(P=3.44×10^(-25))and mesenchymal development(P=2.60×10^(-13)).Regression analysis was conducted to study molecular markers of tobacco exposure.CDCA7L was the most significant gene correlated with cotinine level after adjusting for confounding factors(FDR=0.046).Conclusion The pathways and the possible molecular mechanisms that pregnant women and foetuses may be affected by tobacco exposure are explored and discussed,and the ideas for future molecular mechanism research are proposed.