Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 44033, South Korea.
Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, 90095, USA.
Environ Res. 2021 May;196:110823. doi: 10.1016/j.envres.2021.110823. Epub 2021 Feb 4.
Previously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring.
To identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD.
We obtained stored mid-pregnancy serum from 214 mothers who lived in California's Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman's average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 μm) during the first trimester using the California Line Source Dispersion Model, version 4 (CALINE4). By utilizing liquid chromatography-high resolution mass spectrometry, we identified the metabolic profiles of maternal serum for 116 mothers with offspring who later developed ASD and 98 control mothers. Partial least squares discriminant analysis (PLS-DA) was employed to select metabolic features associated with air pollution exposure or autism risk in offspring. We also conducted extensive pathway enrichment analysis to elucidate potential ASD-related changes in the metabolome of pregnant women.
We extracted 4022 and 4945 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for potential confounders, we identified 167 and 222 discriminative features (HILIC and C18, respectively). Pathway enrichment analysis to discriminate metabolic features associated with ASD risk indicated various metabolic pathway perturbations linked to the tricarboxylic acid (TCA) cycle and mitochondrial function, including carnitine shuttle, amino acid metabolism, bile acid metabolism, and vitamin A metabolism.
Using high resolution metabolomics, we identified several metabolic pathways disturbed in mothers with ASD offspring among women experiencing high exposure to traffic-related air pollution during pregnancy that were associated with mitochondrial dysfunction. These findings provide us with a better understanding of metabolic disturbances involved in the development of ASD under adverse environmental conditions.
先前有大量流行病学研究报告称自闭症谱系障碍（ASD）与孕妇怀孕期间接触空气污染之间存在关联。然而，目前尚无代谢组学研究调查妊娠期间污染暴露对后代 ASD 风险的影响。
确定母体代谢的差异，这些差异可能反映了对暴露于高空气污染的生物学反应，这些母体的后代后来患有或未患有 ASD。
我们从居住在加利福尼亚州中央山谷的 214 名母亲中获得了妊娠中期的储存血清，这些母亲在妊娠早期经历了最高水平的空气污染。我们使用加利福尼亚线源扩散模型第 4 版（CALINE4）估计了每位女性在妊娠早期的平均交通相关空气污染暴露量（一氧化碳、氮氧化物和<2.5μm 的颗粒物）。利用液相色谱-高分辨质谱法，我们鉴定了 116 名后代患有 ASD 的母亲和 98 名对照母亲的母体血清代谢谱。偏最小二乘判别分析（PLS-DA）用于选择与空气污染暴露或后代自闭症风险相关的代谢特征。我们还进行了广泛的途径富集分析，以阐明孕妇代谢组中与 ASD 相关的潜在变化。
我们从亲水作用（HILIC）色谱（正离子模式）和 C18（负离子模式）柱的母体血清样本中分别提取了 4022 种和 4945 种代谢物特征。在控制潜在混杂因素后，我们分别鉴定出 167 种和 222 种具有判别力的特征（HILIC 和 C18）。用于区分与 ASD 风险相关的代谢特征的途径富集分析表明，与三羧酸（TCA）循环和线粒体功能相关的各种代谢途径受到干扰，包括肉碱穿梭、氨基酸代谢、胆汁酸代谢和维生素 A 代谢。
使用高分辨率代谢组学，我们在经历妊娠期间交通相关空气污染高暴露的 ASD 后代母亲中发现了一些与线粒体功能障碍相关的代谢途径紊乱。这些发现使我们更好地了解了在不利环境条件下 ASD 发育过程中涉及的代谢紊乱。
