Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort DOI Creative Commons
Donghai Liang, Kaitlin R. Taibl, Anne L. Dunlop

et al.

Environmental Science & Technology, Journal Year: 2023, Volume and Issue: 57(43), P. 16206 - 16218

Published: Oct. 19, 2023

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

Language: Английский

A review of microbial degradation of per- and polyfluoroalkyl substances (PFAS): Biotransformation routes and enzymes DOI

Ashenafi Berhanu,

Ishmael Mutanda,

Ji Taolin

et al.

The Science of The Total Environment, Journal Year: 2022, Volume and Issue: 859, P. 160010 - 160010

Published: Nov. 8, 2022

Language: Английский

Citations

132
Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program DOI Creative Commons
Amy Padula, Xuejuan Ning, Shivani Bakre

et al.

Environmental Health Perspectives, Journal Year: 2023, Volume and Issue: 131(3)

Published: March 1, 2023

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals associated with risk of adverse birth outcomes. Results previous studies have been inconsistent. Associations between PFAS outcomes may be affected by psychosocial stress. Objectives: We estimated in relation to prenatal concentrations evaluate whether maternal stress modifies those relationships. Methods: included 3,339 participants from 11 prospective cohorts the Environmental influences on Child Health Outcomes (ECHO) program estimate associations five stratified perceived scale scores examine effect modification used Bayesian Weighted Sums mixtures PFAS. Results: observed reduced size increased all For a 1-unit higher log-normalized exposure perfluorooctanoic acid (PFOA), perfluorooctanesulfonic (PFOS), perfluorononanoic (PFNA), perfluorohexane sulfonic (PFHxS), we lower birthweight-for-gestational-age z-scores β=−0.15 [95% confidence interval (CI): −0.27, −0.03], β=−0.14 (95% CI: −0.28, −0.002), β=−0.22 −0.23, −0.10), β=−0.06 −0.18, 0.06), β=−0.25 −0.37, −0.14), respectively. odds ratio (OR) for large-for-gestational-age: ORPFNA=0.56 0.38, 0.83), ORPFDA=0.52 0.35, 0.77). increase concentration summed PFAS, z-score [−0.28; 95% highest posterior density (HPD): −0.44, −0.14] decreased large-for-gestational-age (OR=0.49; HPD: 0.29, 0.82). Perfluorodecanoic (PFDA) explained percentage (40%) both models. were not modified Discussion: Our large, multi-cohort study found negative association birthweight-for-gestational-age, different groups high vs. low This can help inform policy reduce exposures environment humans. https://doi.org/10.1289/EHP10723

Language: Английский

Citations

53
Newborn metabolomic signatures of maternal per- and polyfluoroalkyl substance exposure and reduced length of gestation DOI Creative Commons
Kaitlin R. Taibl, Anne L. Dunlop, Dana Boyd Barr

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 30, 2023

Abstract Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- polyfluoroalkyl substances (PFAS) has been reported reduce length gestation, but the underlying mechanisms are unknown. In present study, we characterized molecular signatures prenatal PFAS exposure gestational age at outcomes in newborn dried blood spot metabolome among 267 African American dyads Atlanta, Georgia between 2016 2020. Pregnant people with higher serum perfluorooctanoic acid perfluorohexane sulfonic concentrations had increased odds an After false discovery rate correction, effect on reduced gestation was associated 8 metabolomic pathways 52 metabolites spots, which suggested perturbed tissue neogenesis, neuroendocrine function, redox homeostasis. These explain how gives rise leading cause infant death United States.

Language: Английский

Citations

47
Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk DOI
Zhiping Niu, Zhizhou Duan, Weixiang He

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 471, P. 134312 - 134312

Published: April 16, 2024

Language: Английский

Citations

27
Persistent organic pollutant perfluorooctanoic acid induces alterations in epigenetic modifications of DNA and RNA DOI

Shu-Yi Gu,

Tian Feng,

Fang‐Yin Gang

et al.

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110957 - 110957

Published: Feb. 1, 2025

Language: Английский

Citations

4
Changes in plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with changes in plasma lipids - A longitudinal study over 10 years DOI Creative Commons
Linda Dunder, Peter Lind, Samira Salihović

et al.

Environmental Research, Journal Year: 2022, Volume and Issue: 211, P. 112903 - 112903

Published: Feb. 26, 2022

Associations between per- and polyfluoroalkyl substances (PFAS), mainly PFOS PFOA, increased blood lipids have been reported primarily from cross-sectional studies. The aim of the present study was to investigate associations multiple PFAS in a longitudinal fashion.A total 864 men women aged 70 years free lipid medication were included Prospective Investigation Vasculature Uppsala Seniors (PIVUS) Sweden, 614 404 those reinvestigated at age 75 80. At all three occasions, eight measured plasma using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) high-density (HDL-C) also occasions. Mixed-effects linear regression models used examine relationship changes levels levels.Changes six out investigated positively associated with after adjustment for sex, change body index (BMI), smoking, physical activity, statin use (age same subjects), correction testing. For example, perfluorodecanoic acid (PFDA) (β: 0.23, 95% confidence interval (CI): 0.14 0.32), triglycerides 0.08, CI: 0.04-0.12) HDL-cholesterol 0.04-0.11).In this measurements over 10 both lipids, giving further support role exposure human metabolism.

Language: Английский

Citations

69
Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes DOI
Josephine M. Brown-Leung, Jason R. Cannon

Chemical Research in Toxicology, Journal Year: 2022, Volume and Issue: 35(8), P. 1312 - 1333

Published: Aug. 3, 2022

Per- and polyfluoroalkyl substances (PFAS) are a group of persistent environmental pollutants that ubiquitously found in the environment virtually all living organisms, including humans. PFAS cross blood–brain barrier accumulate brain. Thus, likely risk for neurotoxicity. Studies measured levels brains humans, polar bears, rats have demonstrated some areas brain greater amounts PFAS. Moreover, there is evidence exposure associated with attention-deficit/hyperactivity disorder (ADHD) children an increased cause death from Parkinson's disease Alzheimer's elderly populations. Given possible links to neurological disease, critical analyses mechanisms neurotoxic action necessary advance field. This paper critically reviews studies investigated potential mechanistic causes neurotoxicity (1) change neurotransmitter levels, (2) dysfunction synaptic calcium homeostasis, (3) alteration neuronal protein expression function. We growing through disruption neurotransmission, particularly dopamine glutamate systems, which implicated age-related psychiatric illnesses neurodegenerative diseases. Evaluated research has shown highly reproduced hippocampus catecholamine hypothalamus decreased whole after exposure. There significant gaps literature relative assessment nigrostriatal system (striatum ventral midbrain) among other regions PFAS-associated neurologic observed In conclusion, suggests may be chronic it imperative future assess impact mixtures on mechanism neurotransmission consequential functional effects.

Language: Английский

Citations

57
Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with oxidative stress biomarkers during pregnancy DOI Creative Commons
Kaitlin R. Taibl,

Susan L. Schantz,

Max T. Aung

et al.

Environment International, Journal Year: 2022, Volume and Issue: 169, P. 107541 - 107541

Published: Sept. 27, 2022

Oxidative stress from excess reactive oxygen species (ROS) is a hypothesized contributor to preterm birth. Per- and polyfluoroalkyl substances (PFAS) exposure reported generate ROS in laboratory settings, linked adverse birth outcomes globally. However, our knowledge, the relationship between PFAS oxidative has not been examined context of human pregnancy.To investigate associations prenatal biomarkers among pregnant people.Our analytic sample included 428 participants enrolled Illinois Kids Development Study Chemicals In Our Bodies prospective cohorts 2014 2019. Twelve were measured second trimester serum. We focused on seven that detected >65 % participants. Urinary levels 8-isoprostane-prostaglandin-F2α, prostaglandin-F2α, 2,3-dinor-8-iso-PGF2α, 2,3-dinor-5,6-dihydro-8-iso-PGF2α third trimesters as stress. fit linear mixed-effects models estimate individual biomarkers. used quantile g-computation Bayesian kernel machine regression (BKMR) assess mixture averaged biomarkers.Linear showed an interquartile range increase perfluorooctane sulfonic acid (PFOS) was associated with 8-isoprostane-prostaglandin-F2α (β = 0.10, 95 confidence interval 0, 0.20). both BKMR, across all biomarkers, PFOS contributed most overall effect. The six remaining significantly changes biomarkers.Our study first during pregnancy. found elevated stress, which consistent prior work animal cell lines. Future research needed understand how maternal may affect fetal development.

Language: Английский

Citations

57
Determinants of maternal and neonatal PFAS concentrations: a review DOI Creative Commons
Jordan McAdam, Erin M. Bell

Environmental Health, Journal Year: 2023, Volume and Issue: 22(1)

Published: May 10, 2023

Per- and polyfluoroalkyl substances (PFAS) are used for their properties such as stain water resistance. The have been associated with adverse health outcomes in both pregnant mothers infants, including pre-eclampsia low birthweight. A growing body of research suggests that PFAS transferred from mother to fetus through the placenta, leading utero exposure. systematic review was performed using PubMed database search studies evaluating determinants concentrations blood matrices neonates shortly after birth. Studies were included this if an observational study design utilized, exposure at least one analyte measured, measured maternal or neonatal matrices, determinant assessed, results beta estimates provided. We identified 35 inclusion evaluated relationships among factors collected these studies. Parity, breastfeeding history, race country origin, household income had strongest most consistent evidence support roles certain mothers. Reported findings on smoking status, alcohol consumption, pre-pregnancy mass index (BMI) suggest not important neonates. Further into informative consumer product use, detailed dietary information, consumed sources potential is needed. Research critical estimate past exposure, build improved models, further our understanding dose-response relationships, which can influence epidemiological risk assessment evaluations. Given exposed PFAS, it identify understand better implement public interventions populations.

Language: Английский

Citations

41
A State-of-the-Science Review on High-Resolution Metabolomics Application in Air Pollution Health Research: Current Progress, Analytical Challenges, and Recommendations for Future Direction DOI Creative Commons
Donghai Liang, Zhenjiang Li, Jelle Vlaanderen

et al.

Environmental Health Perspectives, Journal Year: 2023, Volume and Issue: 131(5)

Published: May 1, 2023

Background: Understanding the mechanistic basis of air pollution toxicity is dependent on accurately characterizing both exposure and biological responses. Untargeted metabolomics, an analysis small-molecule metabolic phenotypes, may offer improved estimation exposures corresponding health responses to complex environmental mixtures such as pollution. The field remains nascent, however, with questions concerning coherence generalizability findings across studies, study designs analytical platforms. Objectives: We aimed review state research from studies using untargeted high-resolution metabolomics (HRM), highlight areas concordance dissimilarity in methodological approaches reported findings, discuss a path forward for future use this platform research. Methods: conducted state-of-the-science a) summarize recent b) identify gaps peer-reviewed literature opportunities addressing these designs. screened articles published within Pubmed Web Science between 1 January 2005 31 March 2022. Two reviewers independently 2,065 abstracts, discrepancies resolved by third reviewer. Results: identified 47 that applied serum, plasma, whole blood, urine, saliva, or other biospecimens investigate impact human metabolome. Eight hundred sixteen unique features confirmed level-1 -2 evidence were be associated at least one more pollutants. Hypoxanthine, histidine, serine, aspartate, glutamate among 35 metabolites consistently exhibiting associations multiple pollutants 5 independent studies. Oxidative stress inflammation-related pathways—including glycerophospholipid metabolism, pyrimidine methionine cysteine tyrosine tryptophan metabolism—were most commonly perturbed pathways >70% More than 80% not chemically annotated, limiting interpretability findings. Conclusions: Numerous investigations have demonstrated feasibility linking internal dose response. Our existing HRM–air points underlying consistency range sample quantitation methods, extraction algorithms, statistical modeling approaches. Future directions should focus validation via hypothesis-driven protocols technical advances annotation quantification. https://doi.org/10.1289/EHP11851

Language: Английский

Citations

35