有机磷(OP)杀虫剂,包括毒死蜱,对母婴健康有许多有害影响。关于毒死蜱暴露对妊娠和分娩结局毒性的生物学机制和内源性途径的数据有限。在这项研究中,我们测量了尿中毒死蜱代谢物,并使用高分辨率代谢组学(HRM)来确定与泰国孕妇中毒死蜱暴露相关的生物学扰动,他们不同程度地暴露于高水平的OP杀虫剂。
这项研究包括来自亚洲妇女及其后代发展和环境暴露研究(SAWASDEE)的50名参与者。我们使用液相色谱-高分辨率质谱对从参与者收集的前三个月血清样品进行代谢分析,以评估与毒死蜱暴露相关的代谢扰动。我们测量了3,5,6-三氯-2-吡啶醇(TCPy),毒死蜱和甲基毒死蜱的特定代谢产物,在妊娠早期的尿液样本中评估暴露水平。在非靶向代谢组范围的关联研究工作流程之后,我们使用广义线性模型,途径富集分析,和化学注释,以确定与尿TCPy水平相关的重要代谢物和途径。
在50名SAWASDEE参与者中,尿TCPy中位数水平为4.36μgTCPy/g肌酐.总的来说,在控制混杂因素后,发现691种独特的代谢特征与TCPy水平显着相关(p<0.05)。与TCPy相关的代谢特征的通路分析显示24个代谢通路的扰动,与活性氧的产生和细胞损伤密切相关。这些途径包括色氨酸代谢,脂肪酸氧化和过氧化物酶体代谢,细胞色素P450代谢,谷胱甘肽代谢,和维生素B3代谢。我们证实了与TCPy水平相关的25种代谢物的化学特性,包括谷胱甘肽,胱氨酸,花生酸,衣康酸,和烟酰胺腺嘌呤二核苷酸.
与TCPy水平相关的代谢扰动与氧化应激有关,细胞损伤和修复,全身炎症,这最终可能有助于健康结果,包括孩子的神经发育缺陷。这些发现支持敏感生物标志物的未来发展,以调查与怀孕期间农药暴露相关的代谢基础,并了解其与儿童不良结局的联系。
Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this
study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides.
This
study included 50 participants from the
Study of Asian Women and their Offspring\'s Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association
study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels.
In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 μg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide.
The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.