In utero exposures to perfluoroalkyl substances and the human fetal liver metabolome in Scotland: a cross-sectional study DOI Creative Commons
Tuulia Hyötyläinen, Aidan McGlinchey, Samira Salihović

et al.

The Lancet Planetary Health, Journal Year: 2024, Volume and Issue: 8(1), P. e5 - e17

Published: Jan. 1, 2024

BackgroundPerfluoroalkyl and polyfluoroalkyl substances are classed as endocrine disrupting compounds but continue to be used in many products such firefighting foams, flame retardants, utensil coatings, waterproofing of food packaging. Perfluoroalkyl exposure aberrantly modulates lipid, metabolite, bile acid levels, increasing susceptibility onset severity metabolic diseases, diabetes dysfunction-associated steatotic liver disease. To date, most studies humans have focused on perfluoroalkyl-exposure effects adults. In this study we aimed show if perfluoroalkyls present the human fetal they consequences for fetus.MethodsIn cross-sectional study, livers from elective termination pregnancies at Aberdeen Pregnancy Counselling Service, Aberdeen, UK, were analysed by both targeted (bile acids perfluoroalkyl substances) combined untargeted (lipids polar metabolites) mass spectrometry based metabolomic analyses, well with RNA-Seq. Only fetuses normally progressing (determined ultrasound scan before termination), terminated non-medical reasons, women older than 16 years, fluent English, between 11 21 weeks gestation collected. Women exhibiting considerable emotional distress or whose had anomalies identified excluded. Stringent bioinformatic statistical methods partial correlation network analysis, linear regression, pathway analysis applied data investigate association hepatic pathways.FindingsFetuses included collected Dec 2, 2004, Oct 27, 2014. 78 study: all metabolomics (40 female 38 male) 57 RNA-Seq (28 29 male). Metabolites associated these varied gestational age. Conjugated markedly positively 23 amino acids, fatty sugar derivatives inversely exposure, glycolithocholic was quantified perfluoroalkyl. Furthermore, 7α-hydroxy-4-cholesten-3-one, a marker synthesis rate, strongly levels detectable early week 12.InterpretationOur shows direct evidence utero specific key products. Our results provide that potential future consequences, manifests fetus first trimester gestation. profiles changes resemble those observed perinatal exposures. Such exposures already linked susceptibility, initiation, progression, exacerbation wide range diseases.FundingUK Medical Research Council, Horizon Europe Program European Union, Seventh Framework Programme NHS Grampian Endowments grants, Partnership Assessment Risks Chemicals, Swedish Formas, Novo Nordisk Foundation, Academy Finland.

Language: Английский

Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis DOI Creative Commons
E. Jane Costello, Sarah Rock,

Nikos Stratakis

et al.

Environmental Health Perspectives, Journal Year: 2022, Volume and Issue: 130(4)

Published: April 1, 2022

Background: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry consumer products bioaccumulate food webs human tissues, such as the liver. Objective: The objective of this study was conduct a systematic review literature meta-analysis evaluating PFAS injury from rodent epidemiological studies. Methods: PubMed Embase were searched for all studies earliest available indexing year through 1 December 2021 using keywords corresponding injury. For data synthesis, results limited humans rodents assessing following indicators injury: serum alanine aminotransferase (ALT), nonalcoholic fatty disease, steatohepatitis, or steatosis. studies, at least three observational per weighted z-score determine direction significance associations. synthesized qualitatively summarize effect. Results: Our search yielded 85 24 primarily people United States. Studies focused on legacy PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic (PFOS), perfluorononanoic (PFNA), perfluorohexanesulfonic acid. Meta-analyses revealed higher ALT levels PFOA (z-score= 6.20, p<0.001), PFOS 3.55, PFNA 2.27, p=0.023). also aspartate gamma-glutamyl transferase humans. In rodents, exposures consistently resulted Conclusion: There consistent hepatotoxicity supported by associations markers function This identifies need additional research next-generation PFAS, mixtures, early life exposures. https://doi.org/10.1289/EHP10092

Language: Английский

Citations

242
Exposure to environmental contaminants is associated with altered hepatic lipid metabolism in non-alcoholic fatty liver disease DOI Creative Commons
Partho Sen, S. U. Qadri, Panu K. Luukkonen

et al.

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 76(2), P. 283 - 293

Published: Oct. 9, 2021

Recent experimental models and epidemiological studies suggest that specific environmental contaminants (ECs) contribute to the initiation pathology of non-alcoholic fatty liver disease (NAFLD). However, underlying mechanisms linking EC exposure with NAFLD remain poorly understood there is no data on their impact human metabolome. Herein, we hypothesized ECs, particularly perfluorinated alkyl substances (PFAS), impacts metabolism, specifically bile acid metabolism.In a well-characterized cohort 105 individuals, investigated effects metabolism. We characterized (via biopsy) circulating metabolomes using 4 mass spectrometry-based analytical platforms, measured PFAS other ECs in serum. subsequently compared these results an study PPARa-humanized mouse model.PFAS appears associated perturbation key hepatic metabolic pathways previously found altered NAFLD, those related lipid identified stronger associations between metabolome, chemical NAFLD-associated clinical variables (liver fat content, HOMA-IR), females than males. Specifically, observed PFAS-associated upregulation acids, triacylglycerols ceramides, association dysregulated glucose metabolism females. The murine further corroborated our findings, vis-à-vis sex-specific changes.Females may be more sensitive harmful PFAS. Lipid-related changes subsequent secondary interplay metabolism.There increasing evidence contaminants, such as progression it how chemicals Here show processes effect different

Language: Английский

Citations

201
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
Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multiethnic cohort DOI
Jesse A. Goodrich, Douglas I. Walker, Xiangping Lin

et al.

JHEP Reports, Journal Year: 2022, Volume and Issue: 4(10), P. 100550 - 100550

Published: Aug. 8, 2022

Language: Английский

Citations

76
The exposome and liver disease - how environmental factors affect liver health DOI Creative Commons
Robert Barouki,

Michel Samson,

Étienne Blanc

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(2), P. 492 - 505

Published: March 7, 2023

Since the initial development of exposome concept, much effort has been devoted to characterisation through analytical, epidemiological, and toxicological/mechanistic studies. There is now an urgent need link human diseases include exposomics in environment-linked pathologies together with genomics other omics. Liver are particularly well suited for such studies since major functions liver detection, detoxification, elimination xenobiotics, as inflammatory responses. It known that several associated i) addictive behaviours alcohol consumption, smoking, a certain extent dietary imbalance obesity, ii) viral parasitic infections, iii) exposure toxins occupational chemicals. Recent indicate environmental exposures also significantly diseases, these air pollution (particulate matter volatile chemicals), contaminants polyaromatic hydrocarbons, bisphenol A per-and poly-fluorinated substances, physical stressors radiation. Furthermore, microbial metabolites "gut-liver" axis play role diseases. Exposomics poised field pathology. Methodological advances exposomics-metabolomics framework, determination risk factors' genomic epigenomic signatures, cross-species biological pathway analysis should further delineate impact on liver, opening way improved prevention, identification new biomarkers effects, additional therapeutic targets.

Language: Английский

Citations

72
A review of cardiovascular effects and underlying mechanisms of legacy and emerging per- and polyfluoroalkyl substances (PFAS) DOI
Zeng-Jin Wen,

Yi-Jing Wei,

Yifei Zhang

et al.

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 97(5), P. 1195 - 1245

Published: March 22, 2023

Language: Английский

Citations

46
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

45
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
Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk DOI Creative Commons
Jennifer J. Schlezinger, Noyan Gokce

Circulation Research, Journal Year: 2024, Volume and Issue: 134(9), P. 1136 - 1159

Published: April 25, 2024

Conservative estimates by the World Health Organization suggest that at least a quarter of global cardiovascular diseases are attributable to environmental exposures. Associations between air pollution and risk have garnered most headlines strong, but less attention has been paid other omnipresent toxicants in our ecosystem. Perfluoroalkyl polyfluoroalkyl substances (PFASs) man-made chemicals extensively used industrial consumer products worldwide aqueous film-forming foam utilized firefighting. As such, exposure PFAS is essentially ubiquitous. Given long half-lives these degradation-resistant chemicals, virtually, all people carrying body burden PFAS. concerns related growing such National Academies Sciences, Engineering Medicine recommended standards for clinical follow-up individuals with high blood levels, including prioritizing screening dyslipidemia. The link dyslipidemia investigated, evidence associations compelling. However, not only factor which associated. Here, we review epidemiological links concern identified factors disease, overweight/obesity, glucose intolerance, hypertension, dyslipidemia, hyperuricemia. Moreover, potential connections vascular disease atherosclerosis. While observational data support selected cardiac factors, additional research needed establish causation better understand how leads development conditions.

Language: Английский

Citations

22
Associations between per-and polyfluoroalkyl substances (PFAS) and county-level cancer incidence between 2016 and 2021 and incident cancer burden attributable to PFAS in drinking water in the United States DOI Creative Commons
Shiwen Li,

Paulina Oliva,

Lu Zhang

et al.

Journal of Exposure Science & Environmental Epidemiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Abstract Background Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked with various cancers. Assessment of PFAS in drinking water cancers can help inform biomonitoring prevention efforts. Objective To screen for incident cancer (2016–2021) assess associations contamination the US. Methods We obtained county-level age-adjusted incidence from Surveillance, Epidemiology, End Results (SEER) Program. Data on levels public systems were Third (UCMR3; 2013–2015) Fifth (UCMR5; 2023–2024) Unregulated Contaminant Monitoring Rule. UCMR3 measured PFOS, PFOA, PFNA, PFHxS, PFHpA, PFBS. UCMR5 expanded measurements include PFBA, PFHxA, PFPeA, PFPeS. created indicators detection and, UCMR5, concentrations above Maximum Levels (MCLs). MCLs PFOA PFOS are 4 ng/L, PFNA PFHxS 10 ng/L. used Poisson regression models between or MCL violation incidence, adjusting potential confounders. estimated number attributable cases. was associated increased digestive, endocrine, oral cavity/pharynx, respiratory systems. Incidence rate ratios (IRRs) ranged 1.02 1.33. The strongest association observed PFBS cavity/pharynx (IRR: 1.33 [1.04, 1.71]). Among males, urinary, brain, leukemia, soft tissues. females, thyroid, tissue. is contribute 4626 [95% CI: 1,377, 8046] cases per year based data 6864 991, 12,804] UCMR5. Impact statement ecological study examined two waves (2013–2015 2016 2021. found that organ system including lung, digestive system, urinary tissue, thyroid. Some have not widely studied their PFAS. also sex differences risks. This first exposure

Language: Английский

Citations

3