Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, United States of America.
Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, United States of America.
PLoS One. 2022 Aug 30;17(8):e0272794. doi: 10.1371/journal.pone.0272794. eCollection 2022.
Prenatal phthalates exposures have been related to adiposity in peripuberty in a sex-specific fashion. Untargeted metabolomics analysis to assess circulating metabolites offers the potential to characterize biochemical pathways by which early life exposures influence the development of cardiometabolic risk during childhood and adolescence, prior to becoming evident in clinical markers.
Among mother-child dyads from the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, we measured 9 phthalate metabolites and bisphenol A in maternal spot urine samples obtained during each trimester of pregnancy, corrected for urinary specific gravity and natural log-transformed. In 110 boys and 124 girls aged 8-14 years, we used a mass-spectrometry based untargeted metabolomics platform to measure fasting serum metabolites, yielding 572 annotated metabolites. We estimated the associations between trimester-specific urinary toxicants and each serum metabolite, among all children or stratified by sex and adjusting for child age, BMI z-score, and pubertal onset. We accounted for multiple comparisons using a 10% false discovery rate (q<0.1).
Associations between exposures and metabolites were observed among all children and in sex-stratified analyses (q<0.1). First trimester MEP, MiBP, and MCPP were associated with decreased 2-deoxy-D-glucose among all children. Among girls, third trimester concentrations of MECPP, MEHHP, MEHP, and MCPP were associated with 15, 13, 1, and 10 metabolites, respectively, including decreased choline and increased acylcarnitines and saturated FAs (FA). Among boys, third trimester MIBP was positively associated with 9 features including long chain saturated FAs, and second trimester MBzP was inversely associated with thyroxine.
Metabolomics biomarkers may reflect sex- and exposure timing-specific responses to prenatal phthalate exposures manifesting in childhood that may not be detected using standard clinical markers of cardiometabolic risk.
产前邻苯二甲酸酯暴露与青春期前的肥胖有关，且具有性别特异性。非靶向代谢组学分析评估循环代谢物，有可能在临床标志物出现之前，描述早期生活暴露影响儿童和青少年时期心脏代谢风险发展的生化途径。
在墨西哥早期环境暴露与环境毒物（ELEMENT）出生队列的母婴对子中，我们测量了母亲在妊娠每个三个月期间采集的点尿样本中的 9 种邻苯二甲酸代谢物和双酚 A，经尿比重校正和自然对数转换。在 110 名男孩和 124 名 8-14 岁的女孩中，我们使用基于质谱的非靶向代谢组学平台测量了空腹血清代谢物，得到了 572 个注释代谢物。我们估计了特定孕期尿毒物与所有儿童或按性别分层的每个血清代谢物之间的关联，并调整了儿童年龄、BMI z 分数和青春期开始。我们使用 10%的错误发现率（q<0.1）进行了多次比较。
在所有儿童和按性别分层的分析中，暴露和代谢物之间存在关联（q<0.1）。第一孕期 MEP、MiBP 和 MCPP 与所有儿童的 2-脱氧-D-葡萄糖降低有关。在女孩中，第三孕期的 MECPP、MEHHP、MEHP 和 MCPP 分别与 15、13、1 和 10 种代谢物相关，包括降低的胆碱和增加的酰基辅酶 A 和饱和脂肪酸（FA）。在男孩中，第三孕期的 MIBP 与包括长链饱和 FA 在内的 9 种特征呈正相关，第二孕期的 MBzP 与甲状腺素呈负相关。
代谢组学生物标志物可能反映了儿童时期产前邻苯二甲酸酯暴露的性别和暴露时间特异性反应，而这些反应可能无法通过心脏代谢风险的标准临床标志物检测到。
