{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T02:57:45Z","timestamp":1783738665189,"version":"3.55.0"},"reference-count":76,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003509","name":"\u00d6rebro University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003509","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metabolomics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that interferes with multiple biological pathways, with lipid metabolism being particularly vulnerable. Early-life exposure may disrupt hepatic function during development, but the underlying mechanisms are not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      This study investigated how\n                      <jats:italic>in ovo<\/jats:italic>\n                      exposure to PFOA affects hepatic metabolism in the developing chicken embryo, with a focus on identifying altered metabolic pathways and potential mediators of toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fertilized chicken eggs (\n                      <jats:italic>Gallus gallus domesticus<\/jats:italic>\n                      ) were exposed\n                      <jats:italic>in ovo<\/jats:italic>\n                      to six concentrations of PFOA (0\u20135\u00a0\u00b5g\/g egg). Embryonic liver tissues were analysed by comprehensive metabolomic profiling using two complementary ultra-high-performance liquid chromatography\u2013quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) platforms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 499 metabolites, including lipids, bile acids, carboxylic acids, amino acids, and phenolic compounds. PFOA exposure caused dose-dependent disturbances in lipid, bile acid, and amino acid metabolism. Notably, multiple secondary bile acids were detected and found to be strongly affected by PFOA, suggesting a central role of bile acid modulation in mediating its effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In ovo<\/jats:italic>\n                      exposure to PFOA disrupts hepatic metabolism in developing chicken embryos, particularly through alterations in bile acid, lipid, and amino acid pathways. These metabolic changes may impair energy production, endocrine regulation, and organ development, with possible long-term health consequences.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-025-02374-5","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T17:55:49Z","timestamp":1764611749000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Perfluorooctanoic acid disrupts hepatic metabolism in the developing chicken embryo"],"prefix":"10.1007","volume":"22","author":[{"given":"Nikolai","family":"Scherbak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Duberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"Kr\u00e5kstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauli","family":"Tikka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex M.","family":"Dickens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Engwall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Ore\u0161i\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuulia","family":"Hy\u00f6tyl\u00e4inen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"2374_CR1","doi-asserted-by":"crossref","unstructured":"Acevedo, A., Dur\u00e1n, C., Ciucci, S., Gerl, M., & Cannistraci, C. V. (2018). LIPEA: Lipid pathway enrichment analysis. bioRxiv.","DOI":"10.1101\/274969"},{"key":"2374_CR2","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/j.envint.2019.02.047","volume":"126","author":"TL Alderete","year":"2019","unstructured":"Alderete, T. L., Jin, R., Walker, D. I., Valvi, D., Chen, Z., Jones, D. P., Peng, C., Gilliland, F. D., Berhane, K., Conti, D. V., Goran, M. I., & Chatzi, L. (2019). Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis. Environment International, 126, 445\u2013453.","journal-title":"Environment International"},{"key":"2374_CR3","doi-asserted-by":"publisher","first-page":"108820","DOI":"10.1016\/j.envint.2024.108820","volume":"190","author":"A Alijagic","year":"2024","unstructured":"Alijagic, A., Sinisalu, L., Duberg, D., Kotlyar, O., Scherbak, N., Engwall, M., Ore\u0161i\u010d, M., & Hy\u00f6tyl\u00e4inen, T. (2024). Metabolic and phenotypic changes induced by PFAS exposure in two human hepatocyte cell models. Environment International, 190, 108820.","journal-title":"Environment International"},{"issue":"2","key":"2374_CR4","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1111\/j.1467-9280.2009.02279.x","volume":"20","author":"B Auyeung","year":"2009","unstructured":"Auyeung, B., Baron-Cohen, S., Ashwin, E., Knickmeyer, R., Taylor, K., Hackett, G., & Hines, M. (2009). Fetal testosterone predicts sexually differentiated childhood behavior in girls and in boys. Psychological Science, 20(2), 144\u2013148.","journal-title":"Psychological Science"},{"key":"2374_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2019.104700","volume":"62","author":"AC Behr","year":"2020","unstructured":"Behr, A. C., Plinsch, C., Braeuning, A., & Buhrke, T. (2020). Activation of human nuclear receptors by perfluoroalkylated substances (PFAS). Toxicology In Vitro, 62, Article 104700.","journal-title":"Toxicology In Vitro"},{"key":"2374_CR6","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.biochi.2020.07.011","volume":"176","author":"KN Belosludtsev","year":"2020","unstructured":"Belosludtsev, K. N., Belosludtseva, N. V., Kosareva, E. A., Talanov, E. Y., Gudkov, S. V., & Dubinin, M. V. (2020). Itaconic acid impairs the mitochondrial function by the inhibition of complexes II and IV and induction of the permeability transition pore opening in rat liver mitochondria. Biochimie, 176, 150\u2013157.","journal-title":"Biochimie"},{"issue":"11","key":"2374_CR7","doi-asserted-by":"publisher","first-page":"4572","DOI":"10.1007\/s10803-019-04162-2","volume":"49","author":"DA Bilder","year":"2019","unstructured":"Bilder, D. A., Esplin, M. S., Coon, H., Burghardt, P., Clark, E. A. S., Fraser, A., Smith, K. R., Worsham, W., Chappelle, K., Rayner, T., & Bakian, A. V. (2019). Early second trimester maternal serum steroid-related biomarkers associated with autism spectrum disorder. Journal of Autism and Developmental Disorders, 49(11), 4572\u20134583.","journal-title":"Journal of Autism and Developmental Disorders"},{"issue":"1","key":"2374_CR8","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.tox.2011.06.012","volume":"288","author":"JA Bjork","year":"2011","unstructured":"Bjork, J. A., Butenhoff, J. L., & Wallace, K. B. (2011). Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes. Toxicology, 288(1), 8\u201317.","journal-title":"Toxicology"},{"issue":"10","key":"2374_CR9","doi-asserted-by":"publisher","first-page":"107001","DOI":"10.1289\/EHP1612","volume":"125","author":"A Cardenas","year":"2017","unstructured":"Cardenas, A., Gold, D. R., Hauser, R., Kleinman, K. P., Hivert, M. F., Calafat, A. M., Ye, X., Webster, T. F., Horton, E. S., & Oken, E. (2017). Plasma concentrations of per- and polyfluoroalkyl substances at baseline and associations with glycemic indicators and diabetes incidence among High-Risk adults in the diabetes prevention program trial. Environmental Health Perspectives, 125(10), 107001\u2013107001.","journal-title":"Environmental Health Perspectives"},{"key":"2374_CR10","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1146\/annurev-animal-020518-115154","volume":"7","author":"RC Cardoso","year":"2019","unstructured":"Cardoso, R. C., & Padmanabhan, V. (2019). Prenatal steroids and metabolic dysfunction: Lessons from sheep. Annual Review of Animal Biosciences, 7, 337\u2013360.","journal-title":"Annual Review of Animal Biosciences"},{"issue":"1","key":"2374_CR11","volume":"68","author":"J Chong","year":"2019","unstructured":"Chong, J., Wishart, D. S., & Xia, J. (2019). Using metaboanalyst 4.0 for comprehensive and integrative metabolomics data analysis. Nucleic Acids Research, 68(1), Article e86.","journal-title":"Nucleic Acids Research"},{"issue":"2","key":"2374_CR12","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1203\/00006450-198502000-00018","volume":"19","author":"C Colombo","year":"1985","unstructured":"Colombo, C., Roda, A., Roda, E., Buscaglia, M., Dell\u2019agnola, C. A., Filippetti, P., Ronchi, M., & Sereni, F. (1985). Correlation between fetal and maternal serum bile acid concentrations. Pediatric Research, 19(2), 227\u2013231.","journal-title":"Pediatric Research"},{"key":"2374_CR13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.tox.2016.12.007","volume":"378","author":"KP Das","year":"2017","unstructured":"Das, K. P., Wood, C. R., Lin, M. T., Starkov, A. A., Lau, C., Wallace, K. B., Corton, J. C., & Abbott, B. D. (2017). Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis. Toxicology, 378, 37\u201352.","journal-title":"Toxicology"},{"key":"2374_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.595371","volume":"8","author":"AP Delli Bovi","year":"2021","unstructured":"Delli Bovi, A. P., Marciano, F., Mandato, C., Siano, M. A., Savoia, M., & Vajro, P. (2021). Oxidative stress in non-alcoholic fatty liver disease. An updated mini review. Frontiers in Medicine (Lausanne), 8, Article 595371.","journal-title":"Frontiers in Medicine (Lausanne)"},{"key":"2374_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2021.105623","volume":"136","author":"N Dooley","year":"2022","unstructured":"Dooley, N., Ruigrok, A., Holt, R., Allison, C., Tsompanidis, A., Waldman, J., Auyeung, B., Lombardo, M. V., & Baron-Cohen, S. (2022). Is there an association between prenatal testosterone and autistic traits in adolescents? Psychoneuroendocrinology, 136, Article 105623.","journal-title":"Psychoneuroendocrinology"},{"issue":"1","key":"2374_CR16","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.prostaglandins.2006.05.002","volume":"82","author":"X Fang","year":"2007","unstructured":"Fang, X., Dillon, J. S., Hu, S., Harmon, S. D., Yao, J., Anjaiah, S., Falck, J. R., & Spector, A. A. (2007). 20-carboxy-arachidonic acid is a dual activator of peroxisome proliferator-activated receptors \u03b1 and \u03b3. Prostaglandins & Other Lipid Mediators, 82(1), 175\u2013184.","journal-title":"Prostaglandins & Other Lipid Mediators"},{"issue":"1","key":"2374_CR17","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1093\/toxsci\/kft100","volume":"134","author":"A Farhat","year":"2013","unstructured":"Farhat, A., Crump, D., Chiu, S., Williams, K. L., Letcher, R. J., Gauthier, L. T., & Kennedy, S. W. (2013). In ovo effects of two organophosphate flame retardants\u2014TCPP and TDCPP\u2014on pipping success, development, mRNA expression, and thyroid hormone levels in chicken embryos. Toxicological Sciences, 134(1), 92\u2013102.","journal-title":"Toxicological Sciences"},{"key":"2374_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.106087","volume":"145","author":"KJ Fernie","year":"2020","unstructured":"Fernie, K. J., Karouna-Renier, N. K., Letcher, R. J., Schultz, S. L., Peters, L. E., Palace, V., & Henry, P. F. P. (2020). Endocrine and physiological responses of hatchling American kestrels (Falco sparverius) following embryonic exposure to technical short-chain chlorinated paraffins (C10-13). Environment International, 145, Article 106087.","journal-title":"Environment International"},{"issue":"4","key":"2374_CR19","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1177\/0192623314558463","volume":"43","author":"AJ Filgo","year":"2015","unstructured":"Filgo, A. J., Quist, E. M., Hoenerhoff, M. J., Brix, A. E., Kissling, G. E., & Fenton, S. E. (2015). Perfluorooctanoic acid (PFOA)-induced liver lesions in two strains of mice following developmental exposures. PPARalpha is not required. Toxicologic Pathology, 43(4), 558\u2013568.","journal-title":"Toxicologic Pathology"},{"issue":"6","key":"2374_CR20","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1002\/etc.4099","volume":"37","author":"CD Franci","year":"2018","unstructured":"Franci, C. D., Aleksieva, A., Boulanger, E., Brandenburg, J., Johnston, T., Malinova, A., & Head, J. A. (2018). Potency of polycyclic aromatic hydrocarbons in chicken and Japanese quail embryos. Environmental Toxicology and Chemistry, 37(6), 1556\u20131564.","journal-title":"Environmental Toxicology and Chemistry"},{"key":"2374_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2021.130178","volume":"362","author":"T Gazzotti","year":"2021","unstructured":"Gazzotti, T., Sirri, F., Ghelli, E., Zironi, E., Zampiga, M., & Pagliuca, G. (2021). Perfluoroalkyl contaminants in eggs from backyard chickens reared in Italy. Food Chemistry, 362, Article 130178.","journal-title":"Food Chemistry"},{"key":"2374_CR22","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.ecoenv.2018.12.040","volume":"170","author":"D Geng","year":"2019","unstructured":"Geng, D., Musse, A. A., Wigh, V., Carlsson, C., Engwall, M., Ore\u0161i\u010d, M., Scherbak, N., & Hy\u00f6tyl\u00e4inen, T. (2019). Effect of perfluorooctanesulfonic acid (PFOS) on the liver lipid metabolism of the developing chicken embryo. Ecotoxicology and Environmental Safety, 170, 691\u2013698.","journal-title":"Ecotoxicology and Environmental Safety"},{"issue":"45","key":"2374_CR23","doi-asserted-by":"publisher","first-page":"12527","DOI":"10.1021\/acs.jafc.0c04456","volume":"68","author":"B G\u00f6ckener","year":"2020","unstructured":"G\u00f6ckener, B., Eichhorn, M., L\u00e4mmer, R., Kotthoff, M., Kowalczyk, J., Numata, J., Schafft, H., Lahrssen-Wiederholt, M., & B\u00fccking, M. (2020). Transfer of per- and polyfluoroalkyl substances (PFAS) from feed into the eggs of laying hens. Part 1: Analytical results including a modified total oxidizable precursor assay. Journal of Agricultural and Food Chemistry, 68(45), 12527\u201312538.","journal-title":"Journal of Agricultural and Food Chemistry"},{"key":"2374_CR24","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1016\/j.envpol.2019.05.110","volume":"253","author":"MF Guigueno","year":"2019","unstructured":"Guigueno, M. F., Head, J. A., Letcher, R. J., Karouna-Renier, N., Peters, L., Hanas, A. M., & Fernie, K. J. (2019). Early life exposure to Triphenyl phosphate: Effects on thyroid function, growth, and resting metabolic rate of Japanese quail (Coturnix japonica) chicks. Environmental Pollution, 253, 899\u2013908.","journal-title":"Environmental Pollution"},{"key":"2374_CR25","doi-asserted-by":"publisher","first-page":"646","DOI":"10.3389\/fphys.2016.00646","volume":"7","author":"C Guo","year":"2016","unstructured":"Guo, C., Chen, W. D., & Wang, Y. D. (2016). TGR5, not only a metabolic regulator. Frontiers in Physiology, 7, 646.","journal-title":"Frontiers in Physiology"},{"key":"2374_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2022.107159","volume":"162","author":"P Guo","year":"2022","unstructured":"Guo, P., Furnary, T., Vasiliou, V., Yan, Q., Nyhan, K., Jones, D. P., Johnson, C. H., & Liew, Z. (2022). Non-targeted metabolomics and associations with per- and polyfluoroalkyl substances (PFAS) exposure in humans: A scoping review. Environment International, 162, Article 107159.","journal-title":"Environment International"},{"issue":"3","key":"2374_CR27","doi-asserted-by":"publisher","first-page":"279","DOI":"10.2217\/fca-2017-0019","volume":"13","author":"L Han","year":"2017","unstructured":"Han, L., Shen, W. J., Bittner, S., Kraemer, F. B., & Azhar, S. (2017). PPARs: Regulators of metabolism and as therapeutic targets in cardiovascular disease. Part II: PPAR-beta\/delta and PPAR-gamma. Future Cardiology, 13(3), 279\u2013296.","journal-title":"Future Cardiology"},{"key":"2374_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.113695","volume":"258","author":"AK Hanas","year":"2020","unstructured":"Hanas, A. K., Guigueno, M. F., Fernie, K. J., Letcher, R. J., Ste-Marie Chamberland, F., & Head, J. A. (2020). Assessment of the effects of early life exposure to Triphenyl phosphate on fear, boldness, aggression, and activity in Japanese quail (Coturnix japonica) chicks. Environmental Pollution, 258, Article 113695.","journal-title":"Environmental Pollution"},{"key":"2374_CR29","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.scitotenv.2017.12.186","volume":"625","author":"X He","year":"2018","unstructured":"He, X., Liu, Y., Xu, B., Gu, L., & Tang, W. (2018). PFOA is associated with diabetes and metabolic alteration in US men: National health and nutrition examination survey 2003\u20132012. Science of the Total Environment, 625, 566\u2013574.","journal-title":"Science of the Total Environment"},{"issue":"2","key":"2374_CR30","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s00244-005-1002-y","volume":"50","author":"GH Heinz","year":"2006","unstructured":"Heinz, G. H., Hoffman, D. J., Kondrad, S. L., & Erwin, C. A. (2006). Factors affecting the toxicity of methylmercury injected into eggs. Archives of Environmental Contamination and Toxicology, 50(2), 264\u2013279.","journal-title":"Archives of Environmental Contamination and Toxicology"},{"issue":"1\u20132","key":"2374_CR31","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.mce.2009.02.021","volume":"304","author":"EP Hines","year":"2009","unstructured":"Hines, E. P., White, S. S., Stanko, J. P., Gibbs-Flournoy, E. A., Lau, C., & Fenton, S. E. (2009). Phenotypic dichotomy following developmental exposure to perfluorooctanoic acid (PFOA) in female CD-1 mice: Low doses induce elevated serum leptin and insulin, and overweight in mid-life. Molecular and Cellular Endocrinology, 304(1\u20132), 97\u2013105.","journal-title":"Molecular and Cellular Endocrinology"},{"issue":"9","key":"2374_CR32","first-page":"2598","volume":"12","author":"MM Holter","year":"2020","unstructured":"Holter, M. M., Chirikjian, M. K., Govani, V. N., & Cummings, B. P. (2020). TGR5 signaling. Hepatic Metabolic Health Nutrients, 12(9), 2598.","journal-title":"Hepatic Metabolic Health Nutrients"},{"issue":"1","key":"2374_CR33","doi-asserted-by":"publisher","first-page":"e5","DOI":"10.1016\/S2542-5196(23)00257-7","volume":"8","author":"T Hy\u00f6tyl\u00e4inen","year":"2024","unstructured":"Hy\u00f6tyl\u00e4inen, T., McGlinchey, A., Salihovic, S., Schubert, A., Douglas, A., Hay, D. C., O\u2019Shaughnessy, P. J., Iredale, J. P., Shaw, S., Fowler, P. A., & Ore\u0161i\u010d, M. (2024). In utero exposures to perfluoroalkyl substances and the human fetal liver metabolome in Scotland: A cross-sectional study. The Lancet Planetary Health, 8(1), e5\u2013e17.","journal-title":"The Lancet Planetary Health"},{"issue":"2","key":"2374_CR34","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1111\/j.1440-169X.1985.00101.x","volume":"27","author":"I Ii","year":"1985","unstructured":"Ii, I., Kimura, I., & Ozawa, E. (1985). Promotion of myoblast proliferation by hypoxanthine and RNA in chick embryo extract. Development, Growth & Differentiation, 27(2), 101\u2013110.","journal-title":"Development, Growth & Differentiation"},{"key":"2374_CR35","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1007\/s40726-023-00269-4","volume":"9","author":"S India-Aldana","year":"2023","unstructured":"India-Aldana, S., Yao, M., Midya, V., Colicino, E., Chatzi, L., Chu, J., Gennings, C., Jones, D. P., Loos, R. J. F., Setiawan, V. W., Smith, M. R., Walker, R. W., Barupal, D., Walker, D. I., & Valvi, D. (2023). PFAS exposures and the human metabolome. A systematic review of epidemiological studies. Current Pollution Reports, 9, 510\u201368.","journal-title":"Current Pollution Reports"},{"issue":"3","key":"2374_CR36","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13622","volume":"52","author":"A Karkucinska-Wieckowska","year":"2022","unstructured":"Karkucinska-Wieckowska, A., Simoes, I. C. M., Kalinowski, P., Lebiedzinska-Arciszewska, M., Zieniewicz, K., Milkiewicz, P., G\u00f3rska-Ponikowska, M., Pinton, P., Malik, A. N., Krawczyk, M., Oliveira, P. J., & Wieckowski, M. R. (2022). Mitochondria, oxidative stress and nonalcoholic fatty liver disease: A complex relationship. European Journal of Clinical Investigation, 52(3), Article e13622.","journal-title":"European Journal of Clinical Investigation"},{"issue":"29","key":"2374_CR37","doi-asserted-by":"publisher","first-page":"10792","DOI":"10.1021\/acs.est.3c02965","volume":"57","author":"R Kesic","year":"2023","unstructured":"Kesic, R., Elliott, J. E., Elliott, K. H., Lee, S. L., & Maisonneuve, F. (2023). Perfluoroalkyl substances in seabird eggs from canada\u2019s Pacific coast: Temporal trends (1973\u20132019) and interspecific patterns. Environmental Science & Technology, 57(29), 10792\u201310803.","journal-title":"Environmental Science & Technology"},{"issue":"1","key":"2374_CR38","first-page":"74","volume":"11","author":"RC Kolanczyk","year":"2023","unstructured":"Kolanczyk, R. C., Saley, M. R., Serrano, J. A., Daley, S. M., & Tapper, M. A. (2023). PFAS Biotransformation Pathways: A Species Comparison Study Toxics 11(1): 74.","journal-title":"PFAS Biotransformation Pathways: A Species Comparison Study Toxics"},{"issue":"6","key":"2374_CR39","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s00011-019-01231-1","volume":"68","author":"J Korbecki","year":"2019","unstructured":"Korbecki, J., Bobi\u0144ski, R., & Dutka, M. (2019). Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors. Inflammation Research, 68(6), 443\u2013458.","journal-title":"Inflammation Research"},{"key":"2374_CR40","doi-asserted-by":"publisher","first-page":"106627","DOI":"10.1016\/j.envint.2021.106627","volume":"156","author":"Y Li","year":"2021","unstructured":"Li, Y., Lu, X., Yu, N., Li, A., Zhuang, T., Du, L., Tang, S., Shi, W., Yu, H., Song, M., & Wei, S. (2021). Exposure to legacy and novel perfluoroalkyl substance disturbs the metabolic homeostasis in pregnant women and fetuses: A metabolome-wide association study. Environment International, 156, 106627.","journal-title":"Environment International"},{"issue":"2","key":"2374_CR41","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.1542\/neo.4-2-e41","volume":"4","author":"EA Liechty","year":"2003","unstructured":"Liechty, E. A. (2003). Protein and amino acid metabolism in the fetal-placental unit. NeoReviews, 4(2), e41\u2013e51.","journal-title":"NeoReviews"},{"key":"2374_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2023.107977","volume":"176","author":"Y Liu","year":"2023","unstructured":"Liu, Y., Liu, S., Huang, J., Liu, Y., Wang, Q., Chen, J., Sun, L., & Tu, W. (2023). Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae. Environment International, 176, Article 107977.","journal-title":"Environment International"},{"key":"2374_CR43","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.ecoenv.2017.01.040","volume":"139","author":"A Lopez-Antia","year":"2017","unstructured":"Lopez-Antia, A., Dauwe, T., Meyer, J., Maes, K., Bervoets, L., & Eens, M. (2017). High levels of PFOS in eggs of three bird species in the neighbourhood of a fluoro-chemical plant. Ecotoxicology and Environmental Safety, 139, 165\u2013171.","journal-title":"Ecotoxicology and Environmental Safety"},{"issue":"16","key":"2374_CR44","doi-asserted-by":"publisher","first-page":"9800","DOI":"10.1021\/acs.est.9b01608","volume":"53","author":"Y Lu","year":"2019","unstructured":"Lu, Y., Gao, K., Li, X., Tang, Z., Xiang, L., Zhao, H., Fu, J., Wang, L., Zhu, N., Cai, Z., Liang, Y., Wang, Y., & Jiang, G. (2019). Mass spectrometry-based metabolomics reveals occupational exposure to Per- and polyfluoroalkyl substances relates to oxidative Stress, fatty acid \u03b2-Oxidation Disorder, and kidney injury in a manufactory in China. Environmental Science & Technology, 53(16), 9800\u20139809.","journal-title":"Environmental Science & Technology"},{"issue":"7","key":"2374_CR45","doi-asserted-by":"publisher","first-page":"817","DOI":"10.3748\/wjg.15.817","volume":"15","author":"RIR Macias","year":"2009","unstructured":"Macias, R. I. R., Marin, J. J. G., & Serrano, M. A. (2009). Excretion of biliary compounds during intrauterine life. World Journal of Gastroenterology, 15(7), 817\u2013828.","journal-title":"World Journal of Gastroenterology"},{"issue":"1","key":"2374_CR46","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1046\/j.1525-142X.2003.03011.x","volume":"5","author":"CM Markey","year":"2003","unstructured":"Markey, C. M., Coombs, M. A., Sonnenschein, C., & Soto, A. M. (2003). Mammalian development in a changing environment: Exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs. Evolution & Development, 5(1), 67\u201375.","journal-title":"Evolution & Development"},{"key":"2374_CR47","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.reprotox.2019.08.003","volume":"90","author":"KJ Marks","year":"2019","unstructured":"Marks, K. J., Jeddy, Z., Flanders, W. D., Northstone, K., Fraser, A., Calafat, A. M., Kato, K., & Hartman, T. J. (2019). Maternal serum concentrations of perfluoroalkyl substances during pregnancy and gestational weight gain: The Avon longitudinal study of parents and children. Reproductive Toxicology, 90, 8\u201314.","journal-title":"Reproductive Toxicology"},{"issue":"4","key":"2374_CR48","doi-asserted-by":"publisher","first-page":"361","DOI":"10.31887\/DCNS.2016.18.4\/mmccarthy","volume":"18","author":"MM McCarthy","year":"2016","unstructured":"McCarthy, M. M. (2016). Sex differences in the developing brain as a source of inherent risk. Dialogues in Clinical Neuroscience, 18(4), 361\u2013372.","journal-title":"Dialogues in Clinical Neuroscience"},{"key":"2374_CR49","volume":"2019","author":"A McGlinchey","year":"2019","unstructured":"McGlinchey, A., Sinioja, T., Lamichhane, S., Bodin, J., Siljander, H., Geng, D., Carlsson, C., Duberg, D., Ilonen, J., Virtanen, S. M., Dirven, H., Berntsen, H. F., Zimmer, K., Nygaard, U. C., Ore\u0161i\u010d, M., Knip, M., & Hy\u00f6tyl\u00e4inen, T. (2019). Prenatal exposure to environmental chemicals modulates serum phospholipids in newborn infants, increasing later risk of type 1 diabetes. bioRxiv, 2019, Article 588350.","journal-title":"bioRxiv"},{"issue":"2","key":"2374_CR50","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1042\/bj1030472","volume":"103","author":"KA Mitropoulos","year":"1967","unstructured":"Mitropoulos, K. A., & Myant, N. B. (1967). The formation of lithocholic acid, chenodeoxycholic acid and alpha- and beta-muricholic acids from cholesterol incubated with rat-liver mitochondria. The Biochemical Journal, 103(2), 472\u2013479.","journal-title":"The Biochemical Journal"},{"issue":"3","key":"2374_CR51","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/etc.5274","volume":"41","author":"PTTT Nguyen","year":"2022","unstructured":"Nguyen, P. T. T. T., Pag\u00e9-Larivi\u00e8re, F., Williams, K., O\u2019Brien, J., & Crump, D. (2022). Developmental and hepatic gene expression changes in chicken embryos exposed to p-tert-butylphenyl diphenyl phosphate and isopropylphenyl phosphate via egg injection. Environmental Toxicology and Chemistry, 41(3), 739\u2013747.","journal-title":"Environmental Toxicology and Chemistry"},{"issue":"6","key":"2374_CR52","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1080\/15376516.2018.1459992","volume":"28","author":"AR Nisha","year":"2018","unstructured":"Nisha, A. R., Hazilawati, H., Mohd Azmi, M. L., & Noordin, M. M. (2018). The induction of aryl hydrocarbon receptor (AHR) in immune organs of developing chicks by polycyclic aromatic hydrocarbons. Toxicology Mechanisms and Methods, 28(6), 461\u2013466.","journal-title":"Toxicology Mechanisms and Methods"},{"issue":"11","key":"2374_CR53","doi-asserted-by":"publisher","first-page":"10855","DOI":"10.1007\/s11356-016-6285-1","volume":"23","author":"M Nord\u00e9n","year":"2016","unstructured":"Nord\u00e9n, M., Berger, U., & Engwall, M. (2016). Developmental toxicity of PFOS and PFOA in great cormorant (Phalacrocorax carbo sinensis), herring gull (Larus argentatus) and chicken (Gallus gallus domesticus). Environmental Science and Pollution Research, 23(11), 10855\u201310862.","journal-title":"Environmental Science and Pollution Research"},{"issue":"5","key":"2374_CR54","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1007\/s11356-012-0869-1","volume":"19","author":"M Nord\u00e9n","year":"2012","unstructured":"Nord\u00e9n, M., Westman, O., Venizelos, N., & Engwall, M. (2012). Perfluorooctane sulfonate increases \u03b2-oxidation of palmitic acid in chicken liver. Environmental Science and Pollution Research, 19(5), 1859\u20131863.","journal-title":"Environmental Science and Pollution Research"},{"issue":"8","key":"2374_CR55","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1038\/s41596-022-00710-w","volume":"17","author":"Z Pang","year":"2022","unstructured":"Pang, Z., Zhou, G., Ewald, J., Chang, L., Hacariz, O., Basu, N., & Xia, J. (2022). Using metaboanalyst 5.0 for LC\u2013HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data. Nature Protocols, 17(8), 1735\u20131761.","journal-title":"Nature Protocols"},{"key":"2374_CR76","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1186\/1471-2105-11-395","volume":"11","author":"T Pluska","year":"2010","unstructured":"Pluskal, T., Castillo, S., Villar-Briones, A., & Oresic, M. (2010). MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinformatics, 11, 395. https:\/\/doi.org\/10.1186\/1471-2105-11-395","journal-title":"BMC Bioinformatics"},{"issue":"4","key":"2374_CR56","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1177\/0192623314551841","volume":"43","author":"EM Quist","year":"2015","unstructured":"Quist, E. M., Filgo, A. J., Cummings, C. A., Kissling, G. E., Hoenerhoff, M. J., & Fenton, S. E. (2015). Hepatic mitochondrial alteration in CD-1 mice associated with prenatal exposures to low doses of perfluorooctanoic acid (PFOA). Toxicologic Pathology, 43(4), 546\u2013557.","journal-title":"Toxicologic Pathology"},{"key":"2374_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2024.142346","volume":"361","author":"L Ricolfi","year":"2024","unstructured":"Ricolfi, L., Taylor, M. D., Yang, Y., Lagisz, M., & Nakagawa, S. (2024). Maternal transfer of per and polyfluoroalkyl substances (PFAS) in wild birds A systematic review and meta analysis. Chemosphere, 361, Article 142346.","journal-title":"Chemosphere"},{"issue":"3","key":"2374_CR58","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.cbpb.2008.04.003","volume":"150","author":"M Sato","year":"2008","unstructured":"Sato, M., Sato, K., & Furuse, M. (2008). Change in hepatic and plasma bile acid contents and its regulatory gene expression in the chicken embryo. Comparative Biochemistry and Physiology, Part B: Biochemistry & Molecular Biology, 150(3), 344\u2013347.","journal-title":"Comparative Biochemistry and Physiology, Part B: Biochemistry & Molecular Biology"},{"issue":"6","key":"2374_CR59","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1111\/j.1442-200X.2011.03435.x","volume":"53","author":"Y Seki","year":"2011","unstructured":"Seki, Y., Matsushita, M., Kimura, A., Nishiura, H., Aoki, K., Inokuchi, T., Mizuochi, T., Kurosawa, T., Kimura, Y., & Matsuishi, T. (2011). Maternal and fetal circulation of unusual bile acids: A pilot study. Pediatrics International, 53(6), 1028\u20131033.","journal-title":"Pediatrics International"},{"issue":"2","key":"2374_CR75","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.jhep.2021.09.039","volume":"76","author":"P Sen","year":"2022","unstructured":"Sen, P., Qadri, S., Luukkonen, P. K., Ragnarsdottir, O., McGlinchey, A., J\u00e4ntti, S., Juuti, A., Arola,J., Schlezinger, J. J., Webster, T. F., Ore\u0161i\u010d, M., Yki-J\u00e4rvinen, H., & Hy\u00f6tyl\u00e4inen, T. (2022). Exposure to environmental contaminants is associated with alterations in hepatic lipid metabolism in non-alcoholic fatty liver disease. Journal of Hepatology, 76(2), 283\u2013293. https:\/\/doi.org\/10.1016\/j.jhep.2021.09.039","journal-title":"Journal of Hepatology"},{"issue":"32","key":"2374_CR60","doi-asserted-by":"publisher","first-page":"16637","DOI":"10.1016\/S0021-9258(18)37438-6","volume":"263","author":"KD Setchell","year":"1988","unstructured":"Setchell, K. D., Dumaswala, R., Colombo, C., & Ronchi, M. (1988). Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. Journal of Biological Chemistry, 263(32), 16637\u201316644.","journal-title":"Journal of Biological Chemistry"},{"issue":"11","key":"2374_CR61","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s11306-022-01945-0","volume":"18","author":"T Sinioja","year":"2022","unstructured":"Sinioja, T., Bodin, J., Duberg, D., Dirven, H., Berntsen, H. F., Zimmer, K., Nygaard, U. C., Oresic, M., & Hyotylainen, T. (2022). Exposure to persistent organic pollutants alters the serum metabolome in non-obese diabetic mice. Metabolomics, 18(11), 87.","journal-title":"Metabolomics"},{"issue":"12","key":"2374_CR62","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-021-01853-9","volume":"17","author":"L Sinisalu","year":"2021","unstructured":"Sinisalu, L., Yeung, L. W. Y., Wang, J., Pan, Y., Dai, J., & Hy\u00f6tyl\u00e4inen, T. (2021). Prenatal exposure to poly-\/per-fluoroalkyl substances is associated with alteration of lipid profiles in cord-blood. Metabolomics, 17(12), Article 103.","journal-title":"Metabolomics"},{"issue":"5","key":"2374_CR63","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1002\/hep.31483","volume":"72","author":"N Stratakis","year":"2020","unstructured":"Stratakis, N., Conti, D. V., Jin, R., Margetaki, K., Valvi, D., Siskos, A. P., Maitre, L., Garcia, E., Varo, N., Zhao, Y., Roumeliotaki, T., Vafeiadi, M., Urquiza, J., Fern\u00e1ndez-Barr\u00e9s, S., Heude, B., Basagana, X., Casas, M., Fossati, S., Gra\u017eulevi\u010dien\u0117, R., \u2026 Chatzi, L. (2020). Prenatal exposure to perfluoroalkyl substances associated with increased susceptibility to liver injury in children. Hepatology, 72(5), 1758\u20131770.","journal-title":"Hepatology"},{"issue":"3","key":"2374_CR64","doi-asserted-by":"publisher","DOI":"10.1289\/EHP2619","volume":"126","author":"Q Sun","year":"2018","unstructured":"Sun, Q., Zong, G., Valvi, D., Nielsen, F., Coull, B., & Grandjean, P. (2018). Plasma concentrations of perfluoroalkyl substances and risk of type 2 diabetes: A prospective investigation among U.S. women. Environmental Health Perspectives, 126(3), Article 037001\u2013037001.","journal-title":"Environmental Health Perspectives"},{"key":"2374_CR65","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.870451","author":"C Surugihalli","year":"2022","unstructured":"Surugihalli, C., Farley, L. S., Beckford, R. C., Kamkrathok, B., Liu, H. C., Muralidaran, V., Patel, K., Porter, T. E., & Sunny, N. E. (2022). Remodeling of hepatocyte mitochondrial metabolism and de novo lipogenesis during the embryonic-to-neonatal transition in chickens. Frontiers in Physiology. https:\/\/doi.org\/10.3389\/fphys.2022.870451","journal-title":"Frontiers in Physiology"},{"key":"2374_CR66","doi-asserted-by":"publisher","DOI":"10.3390\/biom10081133","author":"K Sztolsztener","year":"2020","unstructured":"Sztolsztener, K., Chabowski, A., Harasim-Symbor, E., Bielawiec, P., & Konstantynowicz-Nowicka, K. (2020). Arachidonic acid as an early indicator of inflammation during non-alcoholic fatty liver disease development. Biomolecules. https:\/\/doi.org\/10.3390\/biom10081133","journal-title":"Biomolecules"},{"key":"2374_CR67","unstructured":"Team, R. C. (2017). R: A Language and environment for statistical computing. R Foundation for Statistical Computing. Vienna."},{"issue":"5","key":"2374_CR68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v059.i05","volume":"59","author":"D Tingley","year":"2014","unstructured":"Tingley, D., Yamamoto, T., Hirose, K., Keele, L., & Imai, K. (2014). Mediation: R package for causal mediation analysis. Journal of Statistical Software, 59(5), 1\u201338.","journal-title":"Journal of Statistical Software"},{"key":"2374_CR69","doi-asserted-by":"publisher","DOI":"10.3390\/biology11050792","author":"S Todisco","year":"2022","unstructured":"Todisco, S., Santarsiero, A., Convertini, P., De Stefano, G., Gilio, M., Iacobazzi, V., & Infantino, V. (2022). PPAR alpha as a metabolic modulator of the liver: Role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Biology. https:\/\/doi.org\/10.3390\/biology11050792","journal-title":"Biology"},{"issue":"9","key":"2374_CR70","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1002\/mrd.22809","volume":"84","author":"G Wu","year":"2017","unstructured":"Wu, G., Bazer, F. W., Johnson, G. A., Herring, C., Seo, H., Dai, Z., Wang, J., Wu, Z., & Wang, X. (2017). Functional amino acids in the development of the pig placenta. Molecular Reproduction and Development, 84(9), 870\u2013882.","journal-title":"Molecular Reproduction and Development"},{"key":"2374_CR71","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.neuro.2017.01.001","volume":"59","author":"MS Yu","year":"2017","unstructured":"Yu, M. S., Eng, M. L., Williams, T. D., Guigueno, M. F., & Elliott, J. E. (2017). Assessment of neuroanatomical and behavioural effects of in ovo methylmercury exposure in zebra finches (Taeniopygia guttata). Neurotoxicology, 59, 33\u201339.","journal-title":"Neurotoxicology"},{"issue":"1","key":"2374_CR72","doi-asserted-by":"publisher","DOI":"10.1038\/srep23963","volume":"6","author":"N Yu","year":"2016","unstructured":"Yu, N., Wei, S., Li, M., Yang, J., Li, K., Jin, L., Xie, Y., Giesy, J. P., Zhang, X., & Yu, H. (2016). Effects of perfluorooctanoic acid on metabolic profiles in brain and liver of mouse revealed by a high-throughput targeted metabolomics approach. Scientific Reports, 6(1), Article 23963.","journal-title":"Scientific Reports"},{"key":"2374_CR73","doi-asserted-by":"publisher","first-page":"144099","DOI":"10.1016\/j.chemosphere.2025.144099","volume":"373","author":"S Yu","year":"2025","unstructured":"Yu, S., Kruse, S., & Fuchsman, P. (2025). Critical review: Considerations in applying avian egg injection studies to characterize effects of hydrophobic organic compounds on wild birds. Chemosphere, 373, 144099.","journal-title":"Chemosphere"},{"key":"2374_CR74","doi-asserted-by":"publisher","first-page":"104441","DOI":"10.1016\/j.ebiom.2023.104441","volume":"88","author":"J Zhao","year":"2023","unstructured":"Zhao, J., Stewart, I. D., Baird, D., Mason, D., Wright, J., Zheng, J., GauntT, R., EvansD, M., FreathyR, M., Langenberg, C., Warrington, N. M., Lawlor, D. A., & Borges, M. C. (2023). Causal effects of maternal Circulating amino acids on offspring birthweight: A Mendelian randomisation study. EBioMedicine, 88, 104441.","journal-title":"EBioMedicine"}],"container-title":["Metabolomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11306-025-02374-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11306-025-02374-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11306-025-02374-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:02:04Z","timestamp":1780045324000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11306-025-02374-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":76,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["2374"],"URL":"https:\/\/doi.org\/10.1007\/s11306-025-02374-5","relation":{},"ISSN":["1573-3890"],"issn-type":[{"value":"1573-3890","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"assertion":[{"value":"5 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11"}}