A realistic mixture of ubiquitous persistent organic pollutants affects bone and cartilage development in zebrafish by interaction with nuclear receptor signaling.
Guerrero Limon, Gustavo; Zappia, Jérémie; Muller, Marc
[en] "Persistent organic pollutants (POPs)" have a plethora of deleterious effects on humans and the environment due to their bioaccumulative, persistent, and mimicking properties. Individually, each of these chemicals has been tested and its effects measured, however they are rather found as parts of complex mixtures of which we do not fully grasp the extent of their potential consequences. Here we studied the effects of realistic, environmentally relevant mixtures of 29 POPs on cartilage and bone development using zebrafish as a model species. We observed developmental issues in cartilage, in the form of diverse malformations such as micrognathia, reduced size of the Meckel's and other structures. Also, mineralized bone formation was disrupted, hence impacting the overall development of the larvae at later life stages. Assessment of the transcriptome revealed disruption of nuclear receptor pathways, such as androgen, vitamin D, and retinoic acid, that may explain the mechanisms of action of the compounds within the tested mixtures. In addition, clustering of the compounds using their chemical signatures revealed structural similarities with the model chemicals vitamin D and retinoic acid that can explain the effects and/or enhancing the phenotypes we witnessed. Further mechanistic studies will be required to fully understand this kind of molecular interactions and their repercussions in organisms. Our results contribute to the already existing catalogue of deleterious effects caused by exposure to POPs and help to understand the potential consequences in at risk populations.
Zappia, Jérémie ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Muller, Marc ; Université de Liège - ULiège > GIGA > GIGA Cancer - Molecular Angiogenesis Laboratory
Language :
English
Title :
A realistic mixture of ubiquitous persistent organic pollutants affects bone and cartilage development in zebrafish by interaction with nuclear receptor signaling.
UNEP, United Nations Environment Programme. An Assessment Report on Issues of Concern: Chemicals and Waste Issues Posing Risks to Human Health and the Environment. https:// wedocsuneporg/bitstream/handle/2050011822/33807/ARICpdf?sequence=1&isAllowed=y. 2020; ISBN No: 978-92-807-3808-7.
Chaine C, Hursthouse AS, McLean B, McLellan I, McMahon B, McNulty J, et al. Recycling Plastics from WEEE: A Review of the Environmental and Human Health Challenges Associated with Brominated Flame Retardants. International Journal of Environmental Research and Public Health. 2022; 19(2):766. https://doi.org/10.3390/ijerph19020766 PMID: 35055588
Kirk AB, Michelsen-Correa S, Rosen C, Martin CF, Blumberg B. PFAS and Potential Adverse Effects on Bone and Adipose Tissue Through Interactions With PPARγ. Endocrinology. 2021; 162(12). Epub 2021/09/05. https://doi.org/10.1210/endocr/bqab194 PMID: 34480479; PubMed Central PMCID: PMC9034324.
United Nations. Stockholm Convention on Persistent Organic Pollutants. Treaty Series. 2006; 2256:119. https://treaties.un.org/doc/Publication/UNTS/Volume%202256/v2256.pdf.
European Parliament and Council. REGULATION (EC) No 850/2004 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 29 April 2004 on persistent organic pollutants and amending Directive 79/117/EEC. Official Journal of the European Union. 2004:L158/7–49.
Guo W, Pan B, Sakkiah S, Yavas G, Ge W, Zou W, et al. Persistent Organic Pollutants in Food: Contamination Sources, Health Effects and Detection Methods. Int J Environ Res Public Health. 2019; 16 (22). Epub 2019/11/14. https://doi.org/10.3390/ijerph16224361 PMID: 31717330; PubMed Central PMCID: PMC6888492.
Gregoraszczuk EL, Ptak A. Endocrine-Disrupting Chemicals: Some Actions of POPs on Female Reproduction. Int J Endocrinol. 2013; 2013:828532. Epub 2013/06/14. https://doi.org/10.1155/2013/ 828532 PMID: 23762054; PubMed Central PMCID: PMC3674739.
Brody JG, Moysich KB, Humblet O, Attfield KR, Beehler GP, Rudel RA. Environmental pollutants and breast cancer: epidemiologic studies. Cancer. 2007; 109(12 Suppl):2667–711. Epub 2007/05/16. https://doi.org/10.1002/cncr.22655 PMID: 17503436.
Sanderson JT. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicol Sci. 2006; 94(1):3–21. Epub 2006/06/30. https://doi.org/10.1093/toxsci/kfl051 PMID: 16807284.
Ljunggren SA, Helmfrid I, Salihovic S, van Bavel B, Wingren G, Lindahl M, et al. Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer. Environ Int. 2014; 65:93–9. Epub 2014/01/30. https://doi.org/10.1016/j.envint.2013.12.017 PMID: 24472825.
Panseri S, Chiesa L, Ghisleni G, Marano G, Boracchi P, Ranghieri V, et al. Persistent organic pollutants in fish: biomonitoring and cocktail effect with implications for food safety. Food Additives & Contaminants: Part A. 2019; 36(4):601–11. https://doi.org/10.1080/19440049.2019.1579926 PMID: 30862267
Esposito M, Canzanella S, Lambiase S, Scaramuzzo A, La Nucara R, Bruno T, et al. Organic pollutants (PCBs, PCDD/Fs, PAHs) and toxic metals in farmed mussels from the Gulf of Naples (Italy): Monitoring and human exposure. Regional Studies in Marine Science. 2020; 40:101497. https://doi.org/10.1016/j.rsma.2020.101497.
Van Oostdam JC, Dewailly E, Gilman A, Hansen JC, Odland JO, Chashchin V, et al. Circumpolar maternal blood contaminant survey, 1994–1997 organochlorine compounds. Sci Total Environ. 2004; 330(1–3):55–70. Epub 2004/08/25. https://doi.org/10.1016/j.scitotenv.2004.02.028 PMID: 15325158.
Knutsen HK, Kvalem HE, Thomsen C, Froshaug M, Haugen M, Becher G, et al. Dietary exposure to brominated flame retardants correlates with male blood levels in a selected group of Norwegians with a wide range of seafood consumption. Mol Nutr Food Res. 2008; 52(2):217–27. Epub 2008/02/05. https://doi.org/10.1002/mnfr.200700096 PMID: 18246586.
Polder A, Skaare JU, Skjerve E, Loken KB, Eggesbo M. Levels of chlorinated pesticides and polychlorinated biphenyls in Norwegian breast milk (2002–2006), and factors that may predict the level of contamination. Sci Total Environ. 2009; 407(16):4584–90. Epub 2009/05/22. https://doi.org/10.1016/j.scitotenv.2009.04.032 PMID: 19457543.
Haug LS, Salihovic S, Jogsten IE, Thomsen C, van Bavel B, Lindstrom G, et al. Levels in food and beverages and daily intake of perfluorinated compounds in Norway. Chemosphere. 2010; 80(10):1137–43. Epub 2010/07/06. https://doi.org/10.1016/j.chemosphere.2010.06.023 PMID: 20599247.
Berntsen HF, Berg V, Thomsen C, Ropstad E, Zimmer KE. The design of an environmentally relevant mixture of persistent organic pollutants for use in in vivo and in vitro studies. Journal of toxicology and environmental health Part A. 2017; 80(16–18):1002–16. Epub 2017/08/31. https://doi.org/10.1080/15287394.2017.1354439 PMID: 28854125.
McComb J, Mills IG, Muller M, Berntsen HF, Zimmer KE, Ropstad E, et al. Human blood-based exposure levels of persistent organic pollutant (POP) mixtures antagonise androgen receptor transactivation and translocation. Environ Int. 2019; 132:105083. Epub 2019/08/31. https://doi.org/10.1016/j.envint.2019.105083 PMID: 31470217.
Doan TQ, Berntsen HF, Verhaegen S, Ropstad E, Connolly L, Igout A, et al. A mixture of persistent organic pollutants relevant for human exposure inhibits the transactivation activity of the aryl hydrocarbon receptor in vitro. Environ Pollut. 2019; 254(Pt B):113098. Epub 2019/09/04. https://doi.org/10.1016/j.envpol.2019.113098 PMID: 31479813.
Yadav A, Amber M, Zosen D, Labba NA, Huiberts EHW, Samulin Erdem J, et al. A human relevant mixture of persistent organic pollutants (POPs) and perfluorooctane sulfonic acid (PFOS) enhance nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Toxicol Lett. 2021; 338:85–96. Epub 2020/12/15. https://doi.org/10.1016/j.toxlet.2020.12.007 PMID: 33309997.
Amber M, Xie Y, Berntsen HF, Zimmer KE, Ropstad E, Verhaegen S, et al. Effects of Defined Mixtures of Persistent Organic Pollutants (POPs) on Pre-lethal Cytotoxicity in the Human A-498 Kidney Cell Line In Vitro. Exposure and Health. 2021; 13:465–75. https://doi.org/10.1007/s12403-021-00396-7
Guerrero-Limón G, Nivelle R, Bich-Ngoc N, Duy-Thanh D, Muller M. A Realistic Mixture of Persistent Organic Pollutants Affects Zebrafish Development, Behavior, and Specifically Eye Formation by Inhibiting the Condensin I Complex. Toxics. 2023; 11(4):357. https://doi.org/10.3390/toxics11040357 PMID: 37112584
Khalil N, Koskela A. Bone as a Target for Endocrine Disruptors. In: Issues in Toxicology No 42 Challenges in Endocrine Disruptor Toxicology and Risk Assessment Eds Mantovani, A; Fucic, A; The Royal Society of Chemistry. 2020:218–34. https://doi.org/10.1039/9781839160738-00218
Brandt I, Högman P-G. Selective binding of aldrin and dieldrin in cartilage. Archives of toxicology. 1980; 45(3):223–6. https://doi.org/10.1007/BF02419002 PMID: 7458671
Inomata ONK, Montone RC, Lara WH, Weber RR, Toledo HHB. Tissue distribution of organochlorine residues–PCBs and pesticides–in Antarctic penguins. Antarctic Science. 1996; 8(3):253–5. Epub 2004/05/12. https://doi.org/10.1017/S0954102096000351
Deprouw C, Courties A, Fini JB, Clerget-Froidevaux MS, Demeneix B, Berenbaum F, et al. Pollutants: a candidate as a new risk factor for osteoarthritis-results from a systematic literature review. RMD Open. 2022; 8(2). Epub 2022/06/15. https://doi.org/10.1136/rmdopen-2021-001983 PMID: 35701010; PubMed Central PMCID: PMC9198696.
Abella V, Santoro A, Scotece M, Conde J, Lopez-Lopez V, Lazzaro V, et al. Non-dioxin-like polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) induce chondrocyte cell death through multiple pathways. Toxicol Lett. 2015; 234(1):13–9. Epub 2015/02/11. https://doi.org/10.1016/j.toxlet.2015.02. 001 PMID: 25659934.
Nakashima K, de Crombrugghe B. Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet. 2003; 19(8):458–66. https://doi.org/10.1016/S0168-9525(03)00176-8 PMID: 12902164.
Li Q, Fan X, Lu W, Sun C, Pei Z, Zhang M, et al. Novel NPR2 Gene Mutations Affect Chondrocytes Function via ER Stress in Short Stature. Cells [Internet]. 2022; 11(8). Available from: https://mdpi-res.com/d_attachment/cells/cells-11-01265/article_deploy/cells-11-01265-v2.pdf?version=1649836665.
Mobasheri A, Rayman MP, Gualillo O, Sellam J, van der Kraan P, Fearon U. The role of metabolism in the pathogenesis of osteoarthritis. Nature Reviews Rheumatology. 2017; 13(5):302–11. https://doi.org/10.1038/nrrheum.2017.50 PMID: 28381830
Marie PJ. Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies. Cellular and Molecular Life Sciences. 2015; 72(7):1347–61. https://doi.org/10.1007/ s00018-014-1801-2 PMID: 25487608
Segner H. Zebrafish (Danio rerio) as a model organism for investigating endocrine disruption. Comp Biochem Physiol C Toxicol Pharmacol. 2009; 149(2):187–95. Epub 2008/10/29. https://doi.org/10.1016/j.cbpc.2008.10.099 PMID: 18955160.
Huang W, Wu T, Au WW, Wu K. Impact of environmental chemicals on craniofacial skeletal development: Insights from investigations using zebrafish embryos. Environmental Pollution. 2021; 286:117541. https://doi.org/10.1016/j.envpol.2021.117541 PMID: 34118758
Sojan JM, Gundappa MK, Carletti A, Gaspar V, Gavaia P, Maradonna F, et al. Zebrafish as a Model to Unveil the Pro-Osteogenic Effects of Boron-Vitamin D3 Synergism. Front Nutr. 2022; 9:868805. Epub 2022/05/17. https://doi.org/10.3389/fnut.2022.868805 PMID: 35571926; PubMed Central PMCID: PMC9105455.
Carletti A, Gavaia PJ, Cancela ML, Laize V. Metabolic bone disorders and the promise of marine osteoactive compounds. Cell Mol Life Sci. 2023; 81(1):11. Epub 2023/12/20. https://doi.org/10.1007/ s00018-023-05033-x PMID: 38117357; PubMed Central PMCID: PMC10733242.
Kimmel CB, DeLaurier A, Ullmann B, Dowd J, McFadden M. Modes of developmental outgrowth and shaping of a craniofacial bone in zebrafish. PLoS One. 2010; 5(3):e9475. Epub 2010/03/12. https://doi.org/10.1371/journal.pone.0009475 PMID: 20221441; PubMed Central PMCID: PMC2832765.
Kimmel CB, Miller CT, Moens CB. Specification and morphogenesis of the zebrafish larval head skeleton. Dev Biol. 2001; 233(2):239–57. Epub 2001/05/05. https://doi.org/10.1006/dbio.2001.0201 PMID: 11336493.
Sojan JM, Raman R, Muller M, Carnevali O, Renn J. Probiotics Enhance Bone Growth and Rescue BMP Inhibition: New Transgenic Zebrafish Lines to Study Bone Health. International journal of molecular sciences. 2022; 23(9). Epub 2022/05/15. https://doi.org/10.3390/ijms23094748 PMID: 35563140; PubMed Central PMCID: PMC9102566.
Aceto J, Nourizadeh-Lillabadi R, Maree R, Dardenne N, Jeanray N, Wehenkel L, et al. Zebrafish bone and general physiology are differently affected by hormones or changes in gravity. PLoS One. 2015; 10(6):e0126928. https://doi.org/10.1371/journal.pone.0126928 PMID: 26061167.
Spoorendonk KM, Peterson-Maduro J, Renn J, Trowe T, Kranenbarg S, Winkler C, et al. Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. Development. 2008; 135 (22):3765–74. Epub 2008/10/18. https://doi.org/10.1242/dev.024034 PMID: 18927155.
Jeradi S, Hammerschmidt M. Retinoic acid-induced premature osteoblast-to-preosteocyte transitioning has multiple effects on calvarial development. Development. 2016; 143(7):1205–16. https://doi.org/10.1242/dev.129189 PMID: 26903503; PubMed Central PMCID: PMC4852491.
Laue K, Pogoda HM, Daniel PB, van Haeringen A, Alanay Y, von Ameln S, et al. Craniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid. Am J Hum Genet. 2011; 89(5):595–606. https://doi.org/10.1016/j.ajhg.2011.09.015 PMID: 22019272; PubMed Central PMCID: PMC3213388.
Linville A, Radtke K, Waxman JS, Yelon D, Schilling TF. Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches. Dev Biol. 2009; 325(1):60–70. Epub 2008/10/ 22. https://doi.org/10.1016/j.ydbio.2008.09.022 PMID: 18929555.
Reijntjes S, Rodaway A, Maden M. The retinoic acid metabolising gene, CYP26B1, patterns the cartilaginous cranial neural crest in zebrafish. Int J Dev Biol. 2007; 51(5):351–60. Epub 2007/07/10. https://doi.org/10.1387/ijdb.062258sr PMID: 17616924.
Laue K, Janicke M, Plaster N, Sonntag C, Hammerschmidt M. Restriction of retinoic acid activity by Cyp26b1 is required for proper timing and patterning of osteogenesis during zebrafish development. Development. 2008; 135(22):3775–87. https://doi.org/10.1242/dev.021238 PMID: 18927157; PubMed Central PMCID: PMC3608526.
Bohnsack BL, Kahana A. Thyroid hormone and retinoic acid interact to regulate zebrafish craniofacial neural crest development. Dev Biol. 2013; 373(2):300–9. Epub 2012/11/21. https://doi.org/10.1016/j.ydbio.2012.11.005 PMID: 23165295; PubMed Central PMCID: PMC3534885.
Fleming A, Sato M, Goldsmith P. High-throughput in vivo screening for bone anabolic compounds with zebrafish. J Biomol Screen. 2005; 10(8):823–31. ISI:000234407000007. https://doi.org/10.1177/ 1087057105279952 PMID: 16234346
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects. Physiological Reviews. 2016; 96(1):365–408. https://doi.org/10.1152/physrev.00014.2015 PMID: 26681795.
Salo AM, Cox H, Farndon P, Moss C, Grindulis H, Risteli M, et al. A connective tissue disorder caused by mutations of the lysyl hydroxylase 3 gene. Am J Hum Genet. 2008; 83(4):495–503. Epub 2008/10/ 07. https://doi.org/10.1016/j.ajhg.2008.09.004 PMID: 18834968; PubMed Central PMCID: PMC2561927.
Bala MM, Bala KA. Severe cases of osteogenesis imperfecta type VIII due to a homozygous mutation in P3H1 (LEPRE1) and review of the literature. Adv Clin Exp Med. 2021; 30(12):1233–8. Epub 2021/ 10/13. https://doi.org/10.17219/acem/141367 PMID: 34637196.
Aro E, Salo AM, Khatri R, Finnilä M, Miinalainen I, Sormunen R, et al. Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I. J Biol Chem. 2015; 290(27):16964–78. Epub 2015/05/24. https://doi.org/10.1074/jbc.M115.662635 PMID: 26001784; PubMed Central PMCID: PMC4505441.
Abdi SAH, Alzahrani A, Alghamdi S, Alquraini A, Alghamdi A. Hexaconazole exposure ravages biosynthesis pathway of steroid hormones: revealed by molecular dynamics and interaction. Toxicology Research. 2021; 11(1):60–76. https://doi.org/10.1093/toxres/tfab113 PMID: 35237412
Huang T, Zhao Y, He J, Cheng H, Martyniuk CJ. Endocrine disruption by azole fungicides in fish: A review of the evidence. Sci Total Environ. 2022; 822:153412. https://doi.org/10.1016/j.scitotenv.2022. 153412 PMID: 35090921
Hermsen SAB, Pronk TE, van den Brandhof E-J, van der Ven LTM, Piersma AH. Concentration-Response Analysis of Differential Gene Expression in the Zebrafish Embryotoxicity Test Following Flusilazole Exposure. Toxicol Sci. 2012; 127(1):303–12. https://doi.org/10.1093/toxsci/kfs092 PMID: 22382673
Souders CL II, Perez-Rodriguez V, El Ahmadie N, Zhang X, Tischuk C, Martyniuk CJ. Investigation into the sub-lethal effects of the triazole fungicide triticonazole in zebrafish (Danio rerio) embryos/larvae. Environmental toxicology. 2020; 35(2):254–67. https://doi.org/10.1002/tox.22862 PMID: 31670470
Park J, Hong T, An G, Park H, Song G, Lim W. Triadimenol promotes the production of reactive oxygen species and apoptosis with cardiotoxicity and developmental abnormalities in zebrafish. Sci Total Environ. 2023; 862:160761. https://doi.org/10.1016/j.scitotenv.2022.160761 PMID: 36502969
Thrikawala S, Mesmar F, Bhattacharya B, Muhsen M, Mukhopadhyay S, Flores S, et al. Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish. Toxicol Sci. 2023; 193 (2):119–30. https://doi.org/10.1093/toxsci/kfad031 PMID: 36951524
Tian S, Teng M, Meng Z, Yan S, Jia M, Li R, et al. Toxicity effects in zebrafish embryos (Danio rerio) induced by prothioconazole. Environmental Pollution. 2019; 255:113269. https://doi.org/10.1016/j.envpol.2019.113269 PMID: 31574395
Kandeel AA, Abdel-karim MA, Tawfik WS. Malformations observed in ALBINO mouse fetuses maternally treated with the antifungal drug "diniconazole". Egyptian Journal of Zoology. 2015; 64(64):33–62. https://doi.org/10.12816/0019284
Gupta R, Polaka S, Rajpoot K, Tekade M, Sharma MC, Tekade RK. Chapter 6—Importance of toxicity testing in drug discovery and research. In: Tekade RK, editor. Pharmacokinetics and Toxicokinetic Considerations. 2: Academic Press; 2022. p. 117–44.
Şişman T, Geyikoğlu F, Atamanalp M. Early life-stage toxicity in zebrafish (Danio rerio) following embryonal exposure to selected polychlorinated biphenyls. Toxicology and Industrial Health. 2007; 23 (9):529–36. https://doi.org/10.1177/0748233708089042 PMID: 18681238.
Macaulay LJ, Chen A, Rock KD, Dishaw LV, Dong W, Hinton DE, et al. Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptor β. Aquat Toxicol. 2015; 168:38–47. https://doi.org/10.1016/j.aquatox.2015.09.007.
Lee D-H, Steffes M, Jacobs DR. Positive Associations of Serum Concentration of Polychlorinated Biphenyls or Organochlorine Pesticides with Self-Reported Arthritis, Especially Rheumatoid Type, in Women. Environ Health Persp. 2007; 115(6):883–8. https://doi.org/10.1289/ehp.9887 PMID: 17589595
Daugaard-Petersen T, Langebæk R, Rigét FF, Dyck M, Letcher RJ, Hyldstrup L, et al. Persistent organic pollutants and penile bone mineral density in East Greenland and Canadian polar bears (Ursus maritimus) during 1996–2015. Environment International. 2018; 114:212–8. https://doi.org/10.1016/j.envint.2018.02.022 PMID: 29522985
Rignell-Hydbom A, Skerfving S, Lundh T, Lindh CH, Elmståhl S, Bjellerup P, et al. Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women. Environmental Research. 2009; 109(8):991–6. https://doi.org/10.1016/j.envres.2009.08.008 PMID: 19733845
Hodgson S, Thomas L, Fattore E, Lind PM, Alfven T, Hellström L, et al. Bone Mineral Density Changes in Relation to Environmental PCB Exposure. Environ Health Persp. 2008; 116(9):1162–6. https://doi.org/10.1289/ehp.11107 PMID: 18795157
Lundberg R, Lyche JL, Ropstad E, Aleksandersen M, Rönn M, Skaare JU, et al. Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring. Toxicology. 2006; 228(1):33–40. https://doi.org/10.1016/j.tox.2006.08.016 PMID: 17007988
Koskela A, Koponen J, Lehenkari P, Viluksela M, Korkalainen M, Tuukkanen J. Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation. Scientific reports. 2017; 7(1):6841. https://doi.org/10.1038/s41598-017-07359-6 PMID: 28754927
Khalil N, Ebert JR, Honda M, Lee M, Nahhas RW, Koskela A, et al. Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in obese 8–12 year old children: A pilot study. Environmental Research. 2018; 160:314–21. https://doi.org/10.1016/j.envres.2017.10.014 PMID: 29040951
Jeddy Z, Tobias JH, Taylor EV, Northstone K, Flanders WD, Hartman TJ. Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17. Archives of Osteoporosis. 2018; 13(1):84. https://doi.org/10.1007/s11657-018-0498-5 PMID: 30076472
Koskela A, Finnilä MA, Korkalainen M, Spulber S, Koponen J, Håkansson H, et al. Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation. Toxicology and Applied Pharmacology. 2016; 301:14–21. https://doi.org/10.1016/j.taap.2016.04. 002 PMID: 27068293
Khalil N, Chen A, Lee M, Czerwinski SA, Ebert JR, DeWitt JC, et al. Association of Perfluoroalkyl Substances, Bone Mineral Density, and Osteoporosis in the U.S. Population in NHANES 2009–2010. Environ Health Perspect. 2016; 124(1):81–7. https://doi.org/10.1289/ehp.1307909 PMID: 26058082; PubMed Central PMCID: PMC4710590.
Buckley JP, Kuiper JR, Lanphear BP, Calafat AM, Cecil KM, Chen A, et al. Associations of Maternal Serum Perfluoroalkyl Substances Concentrations with Early Adolescent Bone Mineral Content and Density: The Health Outcomes and Measures of the Environment (HOME) Study. Environ Health Persp. 2021; 129(9):097011. https://doi.org/10.1289/EHP9424 PMID: 34585601
Højsager FD, Andersen M, Juul A, Nielsen F, Möller S, Christensen HT, et al. Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense child cohort. Environment International. 2022; 167:107417. https://doi.org/10.1016/j.envint.2022.107417 PMID: 35914335
Fushimi S, Wada N, Nohno T, Tomita M, Saijoh K, Sunami S, et al. 17β-Estradiol inhibits chondrogenesis in the skull development of zebrafish embryos. Aquat Toxicol. 2009; 95(4):292–8. https://doi.org/10.1016/j.aquatox.2009.03.004.
Cohen SP, LaChappelle AR, Walker BS, Lassiter CS. Modulation of estrogen causes disruption of craniofacial chondrogenesis in Danio rerio. Aquat Toxicol. 2014; 152:113–20. https://doi.org/10.1016/j.aquatox.2014.03.028 PMID: 24747083
Burns FR, Peterson RE, Heideman W. Dioxin disrupts cranial cartilage and dermal bone development in zebrafish larvae. Aquat Toxicol. 2015; 164:52–60. Epub 2015/04/29. https://doi.org/10.1016/j.aquatox.2015.04.005 PMID: 25914093; PubMed Central PMCID: PMC4470709.
Elfawy HA, Anupriya S, Mohanty S, Patel P, Ghosal S, Panda PK, et al. Molecular toxicity of Benzo(a) pyrene mediated by elicited oxidative stress infer skeletal deformities and apoptosis in embryonic zebrafish. Sci Total Environ. 2021; 789:147989. Epub 2021/07/30. https://doi.org/10.1016/j.scitotenv.2021.147989 PMID: 34323819.
Chen J-F, Lin P-W, Tsai Y-R, Yang Y-C, Kang H-Y. Androgens and Androgen Receptor Actions on Bone Health and Disease: From Androgen Deficiency to Androgen Therapy. Cells. 2019; 8(11):1318. https://doi.org/10.3390/cells8111318 PMID: 31731497
Syversen U, Stunes AK, Gustafsson BI, Obrant KJ, Nordsletten L, Berge R, et al. Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone. BMC Endocrine Disorders. 2009; 9(1):10. https://doi.org/10.1186/1472-6823-9-10 PMID: 19331671
Amrein K, Scherkl M, Hoffmann M, Neuwersch-Sommeregger S, Köstenberger M, Tmava Berisha A, et al. Vitamin D deficiency 2.0: an update on the current status worldwide. European Journal of Clinical Nutrition. 2020; 74(11):1498–513. https://doi.org/10.1038/s41430-020-0558-y PMID: 31959942
Pacifici M. Retinoid roles and action in skeletal development and growth provide the rationale for an ongoing heterotopic ossification prevention trial. Bone. 2018; 109:267–75. Epub 2017/08/23. https://doi.org/10.1016/j.bone.2017.08.010 PMID: 28826842; PubMed Central PMCID: PMC8011837.
Huitema LF, Apschner A, Logister I, Spoorendonk KM, Bussmann J, Hammond CL, et al. Entpd5 is essential for skeletal mineralization and regulates phosphate homeostasis in zebrafish. Proc Natl Acad Sci U S A. 2012; 109(52):21372–7. Epub 2012/12/14. https://doi.org/10.1073/pnas.1214231110 PMID: 23236130; PubMed Central PMCID: PMC3535636.
Cotti S, Huysseune A, Koppe W, Rücklin M, Marone F, Wölfel EM, et al. More Bone with Less Minerals: The Effects of Dietary Phosphorus on the Zebrafish Skeleton. Bone Reports. 2022; 16:101446. https://doi.org/10.1016/j.bonr.2022.101446
Tonelli F, Bek JW, Besio R, De Clercq A, Leoni L, Salmon P, et al. Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders. Front Endocrinol (Lausanne). 2020; 11:489. Epub 2020/08/ 28. https://doi.org/10.3389/fendo.2020.00489 PMID: 32849280; PubMed Central PMCID: PMC7416647.
Cereto-Massagué A, Ojeda MJ, Valls C, Mulero M, Garcia-Vallvé S, Pujadas G. Molecular fingerprint similarity search in virtual screening. Methods. 2015; 71:58–63. https://doi.org/10.1016/j.ymeth.2014.08.005 PMID: 25132639
Lizarraga LE, Suter GW, Lambert JC, Patlewicz G, Zhao JQ, Dean JL, et al. Advancing the science of a read-across framework for evaluation of data-poor chemicals incorporating systematic and new approach methods. Regulatory Toxicology and Pharmacology. 2023; 137:105293. https://doi.org/10.1016/j.yrtph.2022.105293 PMID: 36414101
Stucki AO, Barton-Maclaren TS, Bhuller Y, Henriquez JE, Henry TR, Hirn C, et al. Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health. Frontiers in Toxicology. 2022; 4. https://doi.org/10.3389/ftox.2022.964553 PMID: 36119357
Barbo N, Stoiber T, Naidenko OV, Andrews DQ. Locally caught freshwater fish across the United States are likely a significant source of exposure to PFOS and other perfluorinated compounds. Environmental Research. 2023; 220:115165. https://doi.org/10.1016/j.envres.2022.115165 PMID: 36584847
Valsecchi S, Babut M, Mazzoni M, Pascariello S, Ferrario C, De Felice B, et al. Per- and Polyfluoroalkyl Substances (PFAS) in Fish from European Lakes: Current Contamination Status, Sources, and Perspectives for Monitoring. Environmental Toxicology and Chemistry. 2021; 40(3):658–76. https://doi.org/10.1002/etc.4815 PMID: 32644251
Letcher RJ, Bustnes JO, Dietz R, Jenssen BM, Jørgensen EH, Sonne C, et al. Exposure and effects assessment of persistent organohalogen contaminants in arctic wildlife and fish. Sci Total Environ. 2010; 408(15):2995–3043. https://doi.org/10.1016/j.scitotenv.2009.10.038 PMID: 19910021
Piskorska-Pliszczynska J, Maszewski S, Warenik-Bany M, Mikolajczyk S, Goraj L. Survey of Persistent Organochlorine Contaminants (PCDD, PCDF, and PCB) in Fish Collected from the Polish Baltic Fishing Areas. The Scientific World Journal. 2012; 2012:973292. https://doi.org/10.1100/2012/973292 PMID: 22593715
Lammer E, Carr GJ, Wendler K, Rawlings JM, Belanger SE, Braunbeck T. Is the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) a potential alternative for the fish acute toxicity test? Comp Biochem Physiol C Toxicol Pharmacol. 2009; 149(2):196–209. Epub 2008/12/20. https://doi.org/10.1016/j.cbpc.2008.11.006 PMID: 19095081.
Westerfield M. THE ZEBRAFISH BOOK, 5th Edition; A guide for the laboratory use of zebrafish (Danio rerio), Eugene, University of Oregon Press. 2007.
Aceto J, Nourizadeh-Lillabadi R, Bradamante S, Maier J, Alestrom P, Van Loon J, et al. Effects of microgravity simulation on zebrafish transcriptomes and bone physiology; exposure starting at 5 days post-fertilization. npj Microgravity. 2016; 2:16010. Epub 7 April 2016. https://doi.org/10.1038/npjmgrav.2016.10 PMID: 28725727
Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2023 update. Nucleic Acids Research. 2022; 51(D1):D1373–D80. https://doi.org/10.1093/nar/gkac956 PMID: 36305812
Yang C, Tarkhov A, Marusczyk J, Bienfait B, Gasteiger J, Kleinoeder T, et al. New Publicly Available Chemical Query Language, CSRML, To Support Chemotype Representations for Application to Data Mining and Modeling. Journal of Chemical Information and Modeling. 2015; 55(3):510–28. https://doi.org/10.1021/ci500667v PMID: 25647539
Kaufman L, Rousseeuw PJ. Agglomerative Nesting (Program AGNES). In: Finding Groups in Data: An Introduction to Cluster Analysis Finding Groups in Data Wiley Series in Probability and Statistics Wiley & Sons, Inc. 1990:199–252. https://doi.org/10.1002/9780470316801.ch5.
R Core Team. R: A language and environment for statistical computing (4.0.2). R Foundation for Statistical Computing, Vienna, Austria. http://wwwr-projectorg/indexhtml (accessed 9 March 2023). 2020.
Maechler M, Rousseeuw P, Struyf A, M H, K H. cluster: Cluster Analysis Basics and Extensions. R package version 214; https://CRANR-projectorg/package=cluster. 2022.
