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孕妇和新生儿中与内分泌干扰化学物质相关的全球代谢组学改变。

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.

作者信息

Puvvula Jagadeesh, Song Lucie C, Zalewska Klaudia J, Alexander Ariel, Manz Kathrine E, Braun Joseph M, Pennell Kurt D, DeFranco Emily A, Ho Shuk-Mei, Leung Yuet-Kin, Huang Shouxiong, Vuong Ann M, Kim Stephani S, Percy Zana, Bhashyam Priyanka, Lee Raymund, Jones Dean P, Tran Vilinh, Kim Dasom V, Calafat Antonia M, Botelho Julianne C, Chen Aimin

机构信息

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

College of Arts & Sciences, University of Pennsylvania, Philadelphia, PA, USA.

出版信息

Metabolomics. 2025 Jan 25;21(1):20. doi: 10.1007/s11306-024-02219-7.

Abstract

BACKGROUND

Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

METHODS

This study included 75 pregnant individuals who delivered at the University of Cincinnati Hospital from 2014 to 2017. We measured maternal urinary biomarkers of paraben/phenol (12), phthalate (13), and phthalate replacements (4) from the samples collected during the delivery visit. Global serum metabolome profiles were analyzed from maternal blood (n = 72) and newborn (n = 63) cord blood samples collected at delivery. Fifteen of the 29 urinary biomarkers were excluded due to low detection frequency or potential exposures during hospital stay. We assessed metabolome-wide associations between 14 maternal urinary biomarkers and maternal/newborn metabolome profiles. Additionally, performed enrichment analysis to identify potential alterations in metabolic pathways.

RESULTS

We observed metabolome-wide associations between maternal urinary concentrations of phthalate metabolites (mono-isobutyl phthalate), phthalate replacements (mono-2-ethyl-5-carboxypentyl terephthalate, mono-2-ethyl-5-hydroxyhexyl terephthalate) and phenols (bisphenol-A, bisphenol-S) and maternal serum metabolome, using q-value < 0.2 as a threshold. Additionally, associations of phthalate metabolites (mono-n-butyl phthalate, monobenzyl phthalate) and phenols (2,5-dichlorophenol, BPA) with the newborn metabolome were noted. Enrichment analyses revealed associations (p-gamma < 0.05) with amino acid, carbohydrate, lipid, glycan, vitamin, and other cofactor metabolism pathways.

CONCLUSION

Maternal paraben, phenol, phthalate, and phthalate replacement biomarker concentrations at delivery were associated with maternal and newborn serum global metabolome.

摘要

背景

孕期接触非持久性内分泌干扰化学物质(EDCs)可能与不良妊娠结局有关。虽然许多EDCs会影响内分泌系统,但其对内分泌相关代谢途径的影响仍不清楚。本研究旨在探讨分娩时与EDC生物标志物相关的整体代谢组变化。

方法

本研究纳入了2014年至2017年在辛辛那提大学医院分娩的75名孕妇。我们从分娩访视时采集的样本中测量了对羟基苯甲酸酯/苯酚(12种)、邻苯二甲酸酯(13种)和邻苯二甲酸酯替代物(4种)的母体尿液生物标志物。对分娩时采集的母体血液(n = 72)和新生儿(n = 63)脐带血样本进行了整体血清代谢组分析。由于检测频率低或住院期间可能的暴露,29种尿液生物标志物中的15种被排除。我们评估了14种母体尿液生物标志物与母体/新生儿代谢组之间的代谢组关联。此外,进行了富集分析以确定代谢途径中的潜在变化。

结果

以q值<0.2为阈值,我们观察到母体尿液中邻苯二甲酸酯代谢物(单异丁基邻苯二甲酸酯)、邻苯二甲酸酯替代物(单2-乙基-5-羧基戊基对苯二甲酸酯、单2-乙基-5-羟基己基对苯二甲酸酯)和酚类(双酚A、双酚S)的浓度与母体血清代谢组之间存在代谢组关联。此外,还注意到邻苯二甲酸酯代谢物(单正丁基邻苯二甲酸酯、单苄基邻苯二甲酸酯)和酚类(2,5-二氯苯酚、双酚A)与新生儿代谢组的关联。富集分析揭示了与氨基酸、碳水化合物、脂质、聚糖、维生素和其他辅助因子代谢途径的关联(p-γ<0.05)。

结论

分娩时母体对羟基苯甲酸酯、酚类、邻苯二甲酸酯和邻苯二甲酸酯替代物生物标志物浓度与母体和新生儿血清整体代谢组有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c679/11762426/b52f5d0d549c/11306_2024_2219_Fig1_HTML.jpg

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