Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women

Tchen, Rachel; Tan, Youran; Barr, Dana Boyd; Ryan, P. Barry; Tran, ViLinh; Li, Zhenjiang; Hu, Yi‐Juan; Smith, Alicia K.; Jones, Dean P.; Dunlop, Anne L.; Liang, Donghai

doi:10.1016/j.envint.2022.107530

Cited by 18 publications

(7 citation statements)

References 85 publications

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“…Pathway enrichment analysis performed by Tchen et al ( 2022 ) showed steroid hormone biosynthesis as one of the significant altered metabolic pathway linked with BPA exposure (Tchen et al 2022 ) indicating a comparable pathway variation in control females of the present investigation. Also as our study indicated, there are certain studies reported that the sphingolipid metabolism, phenylalanine, tyrosine, tryptophan biosynthesis (Yu et al 2021 ), and glutathione metabolism (Zhang et al 2020 ) were perturbed in PCOS females.…”

Section: Discussionsupporting

confidence: 59%

Distinct metabolic signatures in blood plasma of bisphenol A–exposed women with polycystic ovarian syndrome

Prabhu

Vasishta

Bhat

et al. 2023

Environ Sci Pollut Res

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Polycystic ovarian syndrome (PCOS) is a complicated endocrinopathy with an unclear etiology that afflicts fertility status in women. Although the underlying causes and pathophysiology of PCOS are not completely understood, it is suspected to be driven by environmental factors as well as genetic and epigenetic factors. Bisphenol A (BPA) is a weak estrogenic endocrine disruptor known to cause adverse reproductive outcomes in women. A growing relevance supports the notion that BPA may contribute to PCOS pathogenesis. Due to the indeterminate molecular mechanisms of BPA in PCOS endocrinopathy, we sought liquid chromatography with tandem mass spectrometry (LC–MS/MS), a metabolomics strategy that could generate a metabolic signature based on urinary BPA levels of PCOS and healthy individuals. Towards this, we examined urinary BPA levels in PCOS and healthy women by ELISA and performed univariate and chemometric analysis to distinguish metabolic patterns among high and low BPA in PCOS and healthy females, followed by pathway and biomarker analysis employing MetaboAnalyst 5.0. Our findings indicated aberrant levels of certain steroids, sphingolipids, and others, implying considerable disturbances in steroid hormone biosynthesis, linoleic, linolenic, sphingolipid metabolism, and various other pathways across target groups in comparison to healthy women with low BPA levels. Collectively, our findings provide insight into metabolic signatures of BPA-exposed PCOS women, which can potentially improve management strategies and precision medicine.

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Section: Discussionsupporting

confidence: 59%

Distinct metabolic signatures in blood plasma of bisphenol A–exposed women with polycystic ovarian syndrome

Prabhu

Vasishta

Bhat

et al. 2023

Environ Sci Pollut Res

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“…Metabolomics is the systemic study of all metabolites associated with exogenous exposure and endogenous processes, and has emerged as an innovative and powerful analytical platform in environmental epidemiology. , Recent investigations demonstrate the applicability of using metabolomics as a central platform to link human exposure with internal dose and biological response. − Specifically, an increase in circulating concentrations of PFAS has been consistently associated with several endocrine disruption- and oxidative stress-related pathways. ,,− In one of our recent metabolome-wide association studies (MWAS), we also identified and verified several biomechanisms and biomarkers mediating the association between serum PFAS concentrations and fetal growth restriction . Moreover, in two separate analyses within the same pregnant population, we found an inverse association between prenatal exposure to PFAS, modeled as single chemicals and a mixture, with fetal growth measures. , …”

Section: Introductionmentioning

confidence: 73%

“… 18 , 19 Recent investigations demonstrate the applicability of using metabolomics as a central platform to link human exposure with internal dose and biological response. 19 − 24 Specifically, an increase in circulating concentrations of PFAS has been consistently associated with several endocrine disruption- and oxidative stress-related pathways. 15 , 16 , 25 − 27 In one of our recent metabolome-wide association studies (MWAS), we also identified and verified several biomechanisms and biomarkers mediating the association between serum PFAS concentrations and fetal growth restriction.…”

Section: Introductionmentioning

confidence: 99%

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

Liang,

Taibl,

Dunlop

et al. 2023

Environ. Sci. Technol.

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Prenatal exposure to single chemicals belonging to the per-and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in the mother, fetus, and placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed to multiple PFAS, the potential joint effects of PFAS on the metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics to identify metabolites and metabolic pathways perturbed by exposure to a PFAS mixture during pregnancy. Targeted assessment of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS), along with untargeted metabolomics profiling, were conducted on nonfasting serum samples collected from pregnant African Americans at 6−17 weeks gestation. We estimated the overall mixture effect and partial effects using quantile g-computation and single-chemical effects using linear regression. All models were adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, and gestational weeks at sample collection. Our analytic sample included 268 participants and was socioeconomically diverse, with the majority receiving public health insurance (78%). We observed 13.3% of the detected metabolic features were associated with the PFAS mixture (n = 1705, p < 0.05), which was more than any of the single PFAS chemicals. There was a consistent association with metabolic pathways indicative of systemic inflammation and oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, and vitamins A, C, D, and E metabolism) across all metabolome-wide association studies. Twenty-six metabolites were validated against authenticated compounds and associated with the PFAS mixture (p < 0.05). Based on quantile g-computation weights, PFNA contributed the most to the overall mixture effect for γ-aminobutyric acid (GABA), tyrosine, and uracil. In one of the first studies of its kind, we demonstrate the feasibility and utility of using methods designed for exposure mixtures in conjunction with metabolomics to assess the potential joint effects of multiple PFAS chemicals on the human metabolome. We identified more pronounced metabolic perturbations associated with the PFAS mixture than for single PFAS chemicals. Taken together, our findings illustrate the potential for integrating environmental mixture analyses and high-throughput metabolomics to elucidate the molecular mechanisms underlying human health.

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“…We followed an established untargeted metabolome-wide association study (MWAS) workflow, which included 4 major steps: 1 ) metabolomics profiling, 2 ) statistical analysis, 3 ) pathway enrichment analysis, and 4 ) metabolite identification [ 15 , [24] , [25] , [26] , [27] ].…”

Section: Methodsmentioning

confidence: 99%

Human Milk Composition Is Associated with Maternal Body Mass Index in a Cross-Sectional, Untargeted Metabolomics Analysis of Human Milk from Guatemalan Mothers

Sivalogan,

Liang,

Accardi

et al. 2024

Current Developments in Nutrition

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Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women

Cited by 18 publications

References 85 publications

Distinct metabolic signatures in blood plasma of bisphenol A–exposed women with polycystic ovarian syndrome

Distinct metabolic signatures in blood plasma of bisphenol A–exposed women with polycystic ovarian syndrome

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

Human Milk Composition Is Associated with Maternal Body Mass Index in a Cross-Sectional, Untargeted Metabolomics Analysis of Human Milk from Guatemalan Mothers

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