妊娠期PM2.5暴露与血清代谢组的关联

Association between gestational exposure to PM and serum metabolite profile

[背景]母体的代谢性疾病会对子代发育产生不良影响,而PM2.5是一系列妊娠代谢性疾病的危险因素之一,但其影响母体健康的生物学机制尚不明确。[目的]探究妊娠期PM2.5累积暴露与孕妇血清代谢组的关联。[方法]本研究在上海亲子队列进行个体PM2.5暴露测量的329人中随机选取50人,利用个体暴露预测模型计算孕早中期、孕晚期两次采样结束前三个月PM2.5平均暴露浓度,并使用气相色谱-飞行时间质谱(GC-TOF-MS)法、超高效液相色谱-组合型四级杆Orbitrap质谱(UHPLC-QE-MS)法对其相应时期的血清进行代谢组学检测。运用线性混合效应模型探讨妊娠期PM2.5暴露与血清代谢组的关联,并使用mummichog工具及富集分析进行通路分析。[结果]研究对象平均年龄为(29.31±3.83)岁,分别在孕(17.88±0.81)周、孕(32.54±1.26)周时接受孕早中期、孕晚期血清代谢组学检测,检测前三个月PM2.5平均暴露水平分别为(44.03±8.74)、(40.31±6.33)μg·m^(-3)。经混合效应模型分析及错误发现率校正后,GC-TOF-MS以及UHPLC-QE-MS阳、阴离子模式代谢组学检测结果显示分别有19、1903、179个信号峰与妊娠期PM2.5相关。mummichog通路分析及富集分析结果显示,妊娠期PM2.5暴露可以干扰前列腺素的γ亚麻酸合成、白细胞三烯代谢及维生素E代谢通路,以及天冬氨酸代谢、葡糖-丙氨酸循环、丙氨酸代谢及谷胱甘肽代谢等生物学通路。[结论]妊娠期PM2.5暴露会干扰孕妇一些生物学通路的表达,这些通路主要指向氧化应激、炎症反应及脂肪酸代谢。

[Background]PM2.5 may have adverse effects on offspring’s development,and is known to be associated with a series of gestational metabolic disorders.However,the underlying biological mechanism remains unclear.[Objective]This study aims to explore the association between gestational cumulative PM2.5 exposure and serum metabolite profile.[Methods]We randomly selected 50 participants from the Shanghai Maternal-Child Pairs Cohort for the present study.Three-month mean PM2.5 exposure levels before sampling in the firstsecond trimester and in the third trimester were predicted by personal exposure model.Serum metabolite profiles of the same period was measured using both gas chromatography-time-offlight-mass spectrometry(GC-TOF-MS)and ultra-high-performance liquid chromatography-Q exactive orbitrap mass spectrometry(UHPLC-QE-MS).A linear mixed-effect model was employed to examine the association between gestational PM2.5 exposure and serum metabolite profile.A pathway enrichment analysis was performed with mummichog approach.[Results]The participants had an average age of(29.31±3.83)years.Serum metabolite profile was measured at a mean gestational age of(17.88±0.81)and(32.54±1.26)weeks respectively.The corresponding three-month mean PM2.5 exposure levels were(44.03±8.74)and(40.31±6.33)μg·m^(-3),respectively.After false discovery rate adjustment,in the mixed-effect model,by GC-TOF-MS,19 signal peaks were significantly associated with gestational PM2.5 exposure;by UHPLC-QS-MS,1903 positive ion and 179 negative ion signal peaks were associated with gestational PM2.5 exposure.The results of enrichment analysis with mummichog approach identified the enrichment of prostaglandin formation from dihomo gamma-linolenic acid,leukotriene metabolism,and vitamin E metabolism pathways.[Conclusion]Gestational PM2.5 exposure may perturb some metabolic pathways related to oxidative stress,inflammation,and fatty acid metabolism.