Gestational exposure to organophosphate pesticides and maternal urine metabolomic profile in the GENEIDA birth cohort

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2025-08-13 DOI:10.1016/j.etap.2025.104793

Inmaculada López-Flores , Beatriz González-Alzaga , Desirée Romero-Molina , Antonio F. Hernández , Octavio Pérez-Luzardo , Andrea Acosta-Dacal , Ana Macías-Montes , Luis A. Henríquez-Hernández , Luis D. Boada , Dolors Pelegrí , Juan R. González , Marina Lacasaña

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引用次数: 0

Abstract

Early developmental exposure to organophosphate (OP) pesticides has been linked to adverse health effects, though the underlying molecular pathways remain unclear. This study examined urinary metabolomic profiles of 387 pregnant women in their first and third trimesters using UPLC-MS/MS to identify metabolic disruptions associated with OPs exposure measured via dialkyl phosphate (DAPs) metabolites, including total, methyl and ethyl forms. Multiple linear regression models, adjusted for covariates and corrected for multiple comparisons revealed that first trimester OP exposure was significantly associated with 4-pyridoxic acid, a vitamin B6 metabolite. In the third trimester, OP exposure was linked to metabolites related to amino acid metabolism, synaptic function, cytochrome P450-mediated detoxification, cancer and immune pathways. These findings suggest that OP exposure may disrupt maternal metabolic processes during pregnancy, potentially affecting foetal development. This study highlights potential targets for future hypothesis-driven studies and potential interventions to mitigate OP pesticide exposure during pregnancy.

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妊娠期暴露于有机磷农药和孕妇尿液代谢组学在GENEIDA出生队列

尽管潜在的分子途径尚不清楚，但早期发育暴露于有机磷（OP）农药与不良健康影响有关。本研究使用UPLC-MS/MS检测了387名孕早期和孕晚期孕妇的尿液代谢组学特征，通过测量磷酸二烷基酯（DAPs）代谢物（包括总、甲基和乙基形式）来确定与有机磷暴露相关的代谢紊乱。多元线性回归模型，调整了协变量并对多重比较进行了校正，结果显示，妊娠早期OP暴露与维生素B6代谢物4-吡哆酸显著相关。在妊娠晚期，OP暴露与氨基酸代谢、突触功能、细胞色素p450介导的解毒、癌症和免疫途径相关的代谢物有关。这些发现表明，OP暴露可能会破坏孕妇在怀孕期间的代谢过程，潜在地影响胎儿的发育。这项研究强调了未来假设驱动研究的潜在目标和潜在的干预措施，以减轻妊娠期间OP农药暴露。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.