Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study.
Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study.
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DOI：
10.1289/ehp12125
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发表时间：
2023-09
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
--
作者：
对羟基苯甲酸酯存在于从个人护理产品到食品的日常用品中，是一种具有内分泌干扰活性的化学物质，已被证明会影响生殖功能。本研究调查了尿液中对羟基苯甲酸甲酯、对羟基苯甲酸丙酯或对羟基苯甲酸丁酯的浓度是否与围孕期（女性生殖功能的关键窗口期）的尿液代谢组相关。围孕期尿液代谢组的变化可以深入了解对羟基苯甲酸酯影响生育能力的机制。早期妊娠研究是一项由 221 名试图怀孕的女性组成的前瞻性队列，对 42 名参与者的受孕前和受孕后配对尿液样本中的尿液中对羟基苯甲酸酯浓度进行了测量。我们使用超高效液相色谱四极杆飞行时间质谱法进行非靶向和靶向代谢组学分析。我们使用主成分分析、正交偏最小二乘判别分析和排列测试，再加上单变量统计分析，来寻找与两个时间点对羟基苯甲酸酯浓度相关的代谢物。使用有向无环图识别潜在的混杂因素，并使用多变量线性回归调整结果。使用碎片数据鉴定代谢物。七种代谢物与对羟基苯甲酸酯浓度相关（对预测评分的重要性不同，错误发现率已校正）。我们根据代谢组学标准倡议 (MSI) 2 级确定性确定了四种与饮食相关的代谢物，包括来自烟熏香料、葡萄和橄榄油的代谢物。一种代谢物仅被鉴定为类别水平（MSI 3 级）。两种代谢物未鉴定（MSI 级别 4）。调整后，三种代谢物仍然与对羟基苯甲酸甲酯和对羟基苯甲酸丙酯相关，其中两种与饮食有关。内分泌干扰的代谢组学标志物与对羟基苯甲酸酯浓度无关。这项研究发现了尿液中对羟基苯甲酸酯浓度与饮食相关代谢物之间的新关系，但与假设的内分泌干扰途径上的代谢物之间没有关系。它证明了将非目标代谢组学数据与环境暴露信息以及混杂因素的流行病学调整相结合的可行性。研究结果强调了饮食和对羟基苯甲酸酯暴露之间潜在的重要联系，并应用于营养流行病学和饮食暴露评估。 https://doi.org/10.1289/EHP12125
Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. Seven metabolites were associated with paraben concentration (variable importance to projection score , false discovery rate–corrected ). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125
影响因子：
6.7
作者：
Wesselink AK;Weuve J;Fruh V;Bethea TN;Claus Henn B;Harmon QE;Hauser R;Williams PL;Calafat AM;McClean M;Baird DD;Wise LA
通讯作者：
Wise LA
影响因子：
4.6
作者：
Lee Y;Lee E;Yon DK;Jee HM;Baek HS;Lee SW;Cho JY;Han MY
通讯作者：
Han MY
DOI：
10.1038/s41370-020-0227-1
发表时间：
2021-03
影响因子：
4.5
作者：
Rosen Vollmar AK;Johnson CH;Weinberg CR;Deziel NC;Baird DD;Wilcox AJ;Jukic AMZ
通讯作者：
Jukic AMZ