Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
Environ Int. 2022 Nov;169:107530. doi: 10.1016/j.envint.2022.107530. Epub 2022 Sep 17.
Human and animal exposure to bisphenol A (BPA) has been associated with adverse developmental and reproductive effects. The molecular mechanisms by which BPA exposure exerts its effects are not well-understood, even less known about its analogues bisphenol F (BPF). To address these knowledge gaps, we conducted an untargeted metabolome-wide association study (MWAS) to identify metabolic perturbations associated with BPA/BPF exposures in a pregnant African American cohort.
From a subset of study participants enrolled in the Atlanta African American Maternal-Child cohort, we collected both urine samples, for targeted exposure assessment of BPA (N = 230) and BPF (N = 48), and serum samples, for high-resolution metabolomics (HRM) profiling (N = 230), during early pregnancy (8-14 weeks' gestation). Using an established untargeted HRM workflow consisting of MWAS modeling, pathway enrichment analysis, and chemical annotation and confirmation, we investigated the potential metabolic pathways and features associated with BPA/BPF exposures.
The geometric mean creatinine-adjusted concentrations of urinary BPA and BPF were 0.85 ± 2.58 and 0.70 ± 4.71 µg/g creatinine, respectively. After false positive discovery rate correction at 20 % level, 264 and 733 unique metabolic features were significantly associated with urinary BPA and BPF concentrations, representing 10 and 12 metabolic pathways, respectively. Three metabolic pathways, including steroid hormones biosynthesis, lysine and lipoate metabolism, were significantly associated with both BPA and BPF exposure. Using chemical standards, we have confirmed the chemical identity of 16 metabolites significantly associated with BPA or BPF exposure.
Our findings support that exposure to BPA and BPF in pregnant women is associated with the perturbation of aromatic amino acid metabolism, xenobiotics metabolism, steroid biosynthesis, and other amino acid metabolism closely linked to stress responses, inflammation, neural development, reproduction, and weight regulation.
人类和动物接触双酚 A（BPA）已与发育和生殖不良影响相关联。双酚 A 暴露发挥作用的分子机制尚未得到很好的理解，其类似物双酚 F（BPF）的相关信息则更少。为了弥补这些知识空白，我们进行了一项非靶向代谢组学全关联研究（MWAS），以鉴定在一个怀孕的非裔美国人队列中与 BPA/BPF 暴露相关的代谢物变化。
从亚特兰大非裔美国母婴队列中纳入的一部分研究参与者中，我们收集了尿液样本，用于靶向评估 BPA（N=230）和 BPF（N=48）的暴露情况，以及血清样本，用于进行高分辨率代谢组学（HRM）分析（N=230），这些样本均在妊娠早期（8-14 周妊娠）采集。我们采用了一种已建立的非靶向 HRM 工作流程，包括 MWAS 建模、途径富集分析、化学注释和确证，以研究与 BPA/BPF 暴露相关的潜在代谢途径和特征。
尿中 BPA 和 BPF 的几何均数肌酐校正浓度分别为 0.85±2.58µg/g 肌酐和 0.70±4.71µg/g 肌酐。在经过 20%水平的假阳性发现率校正后，与尿中 BPA 和 BPF 浓度显著相关的独特代谢特征分别有 264 个和 733 个，分别代表 10 个和 12 个代谢途径。类固醇激素生物合成、赖氨酸和硫辛酸代谢三个代谢途径与 BPA 和 BPF 的暴露均显著相关。使用化学标准品，我们已经确认了 16 个与 BPA 或 BPF 暴露显著相关的代谢物的化学特征。
我们的研究结果支持这样的观点，即孕妇接触 BPA 和 BPF 与芳香族氨基酸代谢、外源性代谢物代谢、类固醇生物合成以及其他与应激反应、炎症、神经发育、生殖和体重调节密切相关的氨基酸代谢的紊乱有关。
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