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胚胎生长停滞(EGA)与大气细颗粒物污染(PM)之间的关联及孕妇绒毛的空间代谢组学研究。

Study of association between embryo growth arrest (EGA) and atmospheric fine particulate matter pollution (PM) and spatial metabolomics of villi derived from pregnant women.

作者信息

Bai Lirong, Fu Pengfei, Dong Chuan, Li Zhiping, Yue Jianwei, Li Xinling, Cao Qi, Han Yuankun, Zhang Shufen, Li Ruijin

机构信息

Institute of Environmental Science, Shanxi University, Taiyuan, China.

Faculty of Health, York University, Toronto, Canada.

出版信息

J Hazard Mater. 2025 Mar 5;485:136833. doi: 10.1016/j.jhazmat.2024.136833. Epub 2024 Dec 9.

Abstract

Fine particulate matter (PM) is related to embryo growth arrest (EGA). In this study, we collected demographic information from EGA cases and early pregnancy controls in Taiyuan, China, between 2022 and 2023 and obtained villi and serum samples from these participants. We employed multilevel mixed-effects logistic regression models to estimate the odds ratios (ORs). Subsequently, we examined the associations between PM and its components and the EGA-related biomarkers in the serum of the case-control groups. Additionally, we performed spatial metabolomics on villi using mass spectrometry imaging. Our results indicated that PM levels during pregnancy were higher in the EGA group compared to the control, increasing the risk by 17 % (OR=1.17, 95 %CI: 1.06-1.30, p = 0.001). PM and its components (Ni, Pb, ANY, NAP, ANT, PYR, and BaP) showed significant negative correlations with biomarkers (PAPP-A, VEGF, and PROG). Furthermore, EGA induced histopathological changes in the villi alongside differential spatial distribution of metabolites. Key metabolites, including 2'-deoxyinosine triphosphate, cytidine triphosphate, uridine triphosphate, guanosine-5'-triphosphate, guanosine diphosphate, and deoxyguanosine-5'-triphosphate, were predominantly involved in purine and pyrimidine metabolism pathways. It provides evidence of the association between PM and EGA and demonstrates the utility of spatial metabolomics in elucidating the metabolic alterations induced by PM in EGA.

摘要

细颗粒物(PM)与胚胎生长停滞(EGA)有关。在本研究中,我们收集了2022年至2023年期间中国太原EGA病例和早孕对照组的人口统计学信息,并从这些参与者中获取了绒毛和血清样本。我们采用多水平混合效应逻辑回归模型来估计比值比(OR)。随后,我们研究了病例对照组血清中PM及其成分与EGA相关生物标志物之间的关联。此外,我们使用质谱成像对绒毛进行了空间代谢组学分析。我们的结果表明,EGA组孕期的PM水平高于对照组,风险增加了17%(OR=1.17,95%CI:1.06-1.30,p=0.001)。PM及其成分(镍、铅、苊烯、萘、蒽、芘和苯并[a]芘)与生物标志物(妊娠相关血浆蛋白-A、血管内皮生长因子和孕酮)呈显著负相关。此外,EGA导致绒毛出现组织病理学变化以及代谢物的差异空间分布。关键代谢物,包括三磷酸2'-脱氧肌苷、三磷酸胞苷、三磷酸尿苷、三磷酸鸟苷、二磷酸鸟苷和脱氧三磷酸鸟苷,主要参与嘌呤和嘧啶代谢途径。这为PM与EGA之间的关联提供了证据,并证明了空间代谢组学在阐明PM在EGA中诱导的代谢改变方面的效用。

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