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Per- and polyfluoroalkyl substance (PFAS) exposure, maternal metabolomic perturbation, and fetal growth in African American women: A meet-in-the-middle approach
Environment International ( IF 11.8 ) Pub Date : 2021-11-01 , DOI: 10.1016/j.envint.2021.106964
Che-Jung Chang 1 , Dana Boyd Barr 1 , P Barry Ryan 1 , Parinya Panuwet 1 , Melissa M Smarr 1 , Ken Liu 2 , Kurunthachalam Kannan 3 , Volha Yakimavets 1 , Youran Tan 4 , ViLinh Ly 2 , Carmen J Marsit 1 , Dean P Jones 2 , Elizabeth J Corwin 5 , Anne L Dunlop 6 , Donghai Liang 1
Affiliation  

Background

Prenatal exposures to per- and polyfluoroalkyl substances (PFAS) have been linked to reduced fetal growth. However, the detailed molecular mechanisms remain largely unknown. This study aims to investigate biological pathways and intermediate biomarkers underlying the association between serum PFAS and fetal growth using high-resolution metabolomics in a cohort of pregnant African American women in the Atlanta area, Georgia.

Methods

Serum perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) measurements and untargeted serum metabolomics profiling were conducted in 313 pregnant African American women at 8–14 weeks gestation. Multiple linear regression models were applied to assess the associations of PFAS with birth weight and small-for-gestational age (SGA) birth. A high-resolution metabolomics workflow including metabolome-wide association study, pathway enrichment analysis, and chemical annotation and confirmation with a meet-in-the-middle approach was performed to characterize the biological pathways and intermediate biomarkers of the PFAS-fetal growth relationship.

Results

Each log2-unit increase in serum PFNA concentration was significantly associated with higher odds of SGA birth (OR = 1.32, 95% CI 1.07, 1.63); similar but borderline significant associations were found in PFOA (OR = 1.20, 95% CI 0.94, 1.49) with SGA. Among 25,516 metabolic features extracted from the serum samples, we successfully annotated and confirmed 10 overlapping metabolites associated with both PFAS and fetal growth endpoints, including glycine, taurine, uric acid, ferulic acid, 2-hexyl-3-phenyl-2-propenal, unsaturated fatty acid C18:1, androgenic hormone conjugate, parent bile acid, and bile acid-glycine conjugate. Also, we identified 21 overlapping metabolic pathways from pathway enrichment analyses. These overlapping metabolites and pathways were closely related to amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism perturbations.

Conclusion

In this cohort of pregnant African American women, higher serum concentrations of PFOA and PFNA were associated with reduced fetal growth. Perturbations of biological pathways involved in amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism were associated with PFAS exposures and reduced fetal growth, and uric acid was shown to be a potential intermediate biomarker. Our results provide opportunities for future studies to develop early detection and intervention for PFAS-induced fetal growth restriction.



中文翻译:

全氟烷基物质和多氟烷基物质 (PFAS) 暴露、母体代谢组学扰动和非裔美国女性的胎儿生长:一种中间相遇的方法

背景

产前接触全氟烷基物质和多氟烷基物质 (PFAS) 与胎儿生长减慢有关。然而,详细的分子机制在很大程度上仍然未知。本研究旨在使用高分辨率代谢组学研究佐治亚州亚特兰大地区的非洲裔美国孕妇队列中血清 PFAS 与胎儿生长之间关联的生物学途径和中间生物标志物。

方法

对 313 名妊娠 8-14 周的非洲裔美国孕妇进行了血清全氟己烷磺酸 (PFHxS)、全氟辛烷磺酸 (PFOS)、全氟辛酸 (PFOA) 和全氟壬酸 (PFNA) 测量和非靶向血清代谢组学分析。应用多元线性回归模型评估 PFAS 与出生体重和小于胎龄儿 (SGA) 出生的关联。高分辨率代谢组学工作流程包括全代谢组关联研究、通路富集分析、化学注释和中间会合方法确认,以表征 PFAS-胎儿生长关系的生物学通路和中间生物标志物。

结果

每个日志2-血清 PFNA 浓度的单位增加与 SGA 出生的较高几率显着相关(OR = 1.32,95% CI 1.07,1.63);在 PFOA(OR = 1.20,95% CI 0.94,1.49)与 SGA 中发现了相似但临界的显着关联。在从血清样本中提取的 25,516 个代谢特征中,我们成功注释并确认了 10 个与 PFAS 和胎儿生长终点相关的重叠代谢物,包括甘氨酸、牛磺酸、尿酸、阿魏酸、2-己基-3-苯基-2-丙烯醛、不饱和脂肪酸 C18:1、雄激素结合物、母体胆汁酸和胆汁酸-甘氨酸结合物。此外,我们从通路富集分析中确定了 21 条重叠的代谢通路。这些重叠的代谢物和途径与氨基酸、脂质和脂肪酸、胆汁酸、

结论

在这个非裔美国孕妇队列中,较高的 PFOA 和 PFNA 血清浓度与胎儿生长减慢有关。涉及氨基酸、脂质和脂肪酸、胆汁酸和雄激素代谢的生物途径的扰动与 PFAS 暴露和胎儿生长减少有关,尿酸被证明是一种潜在的中间生物标志物。我们的结果为未来的研究提供了机会,以开发针对 PFAS 引起的胎儿生长受限的早期检测和干预。

更新日期:2021-11-01
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