Embryo/larval toxicity and transcriptional effects in zebrafish (Danio rerio) exposed to endocrine active riverbed sediments

  • Luigi ViganòEmail author
  • Nadia Casatta
  • Anna Farkas
  • Giuseppe Mascolo
  • Claudio Roscioli
  • Fabrizio Stefani
  • Matteo Vitelli
  • Fabio Olivo
  • Laura Clerici
  • Pasquale Robles
  • Pierluisa Dellavedova
Research Article


Sediment toxicity plays a fundamental role in the health of inland fish communities; however, the assessment of the hazard potential of contaminated sediments is not a common objective in environmental diagnostics or remediation. This study examined the potential of transcriptional endpoints investigated in zebrafish (Danio rerio) exposed to riverbed sediments in ecotoxicity testing. Embryo-larval 10-day tests were conducted on sediment samples collected from five sites (one upstream and four downstream of the city of Milan) along a polluted tributary of the Po River, the Lambro River. Sediment chemistry showed a progressive downstream deterioration in river quality, so that the final sampling site showed up to eight times higher concentrations of, for example, triclosan, galaxolide, PAH, PCB, BPA, Ni, and Pb, compared with the uppermost site. The embryo/larval tests showed widespread toxicity although the middle river sections evidenced worse effects, as evidenced by delayed embryo development, hatching rate, larval survival, and growth. At the mRNA transcript level, the genes encoding biotransformation enzymes (cyp1a, gst, ugt) showed increasing upregulations after exposure to sediment from further downstream sites. The genes involved in antioxidant responses (sod, gpx) suggested that more critical conditions may be present at downstream sites, but even upstream of Milan there seemed to be some level of oxidative stress. Indirect evidences of potential apoptotic activity (bcl2/bax < 1) in turn suggested the possibility of genotoxic effects. The genes encoding for estrogen receptors (erα, erβ1, erβ2) showed exposure to (xeno)estrogens with a progressive increase after exposure to sediments from downstream sites, paralleled by a corresponding downregulation of the ar gene, likely related to antiandrogenic compounds. Multiple levels of thyroid disruption were also evident particularly in downstream zebrafish, as for thyroid growth (nkx2.1), hormone synthesis and transport (tg, ttr, d2), and signal transduction (trα, trβ). The inhibition of the igf2 gene reasonably reflected larval growth inhibitions. Although none of the sediment chemicals could singly explain fish responses, principal component analysis suggested a good correlation between gene transcripts and the overall trend of contamination. Thus, the combined impacts from known and unknown covarying chemicals were proposed as the most probable explanation of fish responses. In summary, transcriptional endpoints applied to zebrafish embryo/larval test can provide sensitive, comprehensive, and timeliness information which may greatly enable the assessment of the hazard potential of sediments to fish, complementing morphological endpoints and being potentially predictive of longer studies.


Endocrine disruptors Gene expression Embryo-larval toxicity Zebrafish Lambro River sediments Po River 


Funding information

This study received financial support from Regione Lombardia (Progetto Sedimenti Lambro).

Supplementary material

11356_2019_7417_MOESM1_ESM.docx (525 kb)
ESM 1 (DOCX 524 kb)


  1. Ács A, Imre K, Gy K, Csaba J, Győri J, Vehovszky Á, Farkas A (2015) Evaluation of multixenobiotic resistance in dreissenid mussels as a screening tool for toxicity in freshwater sediments. Arch Environ Contam Toxicol 68(4):707–717CrossRefGoogle Scholar
  2. Alvarez-Munoz D, Indiveri P, Rostkowski P, Horwood J, Greer E, Minier C, Popec N, Langston WJ, Hill EM (2015) Widespread contamination of coastal sediments in the transmanche channel with anti-androgenic compounds. Mar Pollut Bull 95:590–597CrossRefGoogle Scholar
  3. Arlos MJ, Bragg LM, Parker WJ, Servos MR (2015) Distribution of selected antiandrogens and pharmaceuticals in a highly impacted watershed. Water Res 72:40–50CrossRefGoogle Scholar
  4. Bemanian V, Male R, Goksøyr A (2004) The aryl hydrocarbon receptor-mediated disruption of vitellogenin synthesis in the fish liver: cross-talk between AHR- and ERalpha-signalling pathways. Comp Hepatol 3:2. CrossRefGoogle Scholar
  5. Birceanu O, Servos MR, Vijayan MM (2015) Bisphenol A accumulation in eggs disrupts the endocrine regulation of growth in rainbow trout larvae. Aquat Toxicol 161:51–60. CrossRefGoogle Scholar
  6. Blazer VS, Iwanowicz LR, Henderson H, Mazik PM, Jenkins JA, Alvarez DA, Young JA (2012) Reproductive endocrine disruption in smallmouth bass (Micropterus dolomieu) in the Potomac River basin: spatial and temporal comparisons of biological effects. Environ Monit Assess 184:4309–4334CrossRefGoogle Scholar
  7. Brian JV, Harris CA, Scholze M, Kortenkamp A, Booy P, Lamoree M, Pojana G, Jonkers N, Marcomini A, Sumpter JP (2007) Evidence of estrogenic mixture effects on the reproductive performance of fish. Environ Sci Technol 41:337–344CrossRefGoogle Scholar
  8. Brown CL, Urbinati EC, Zhang W, Brown SB, McComb-Kobza M (2014) Maternal thyroid and glucocorticoid hormone interactions in larval fish development, and their applications in aquaculture. Reviews in Fisheries Science & Aquaculture 22:207–220CrossRefGoogle Scholar
  9. Casatta N, Stefani F, Viganò L (2017) Hepatic gene expression profiles of a non-model cyprinid (Barbus plebejus) chronically exposed to river sediments. Comp Biochem Physiol Part C, Toxicology and Pharmacology 196:27–35. CrossRefGoogle Scholar
  10. Chan WK, Chan KM (2012) Disruption of the hypothalamic–pituitary–thyroid axis in zebrafish embryo–larvae following waterborne exposure to BDE-47, TBBPA and BPA. Aquat Toxicol 108:106–111CrossRefGoogle Scholar
  11. Chen Q, Yu L, Yang L, Zhou B (2012) Bioconcentration and metabolism of decabromodiphenyl ether (BDE-209) result in thyroid endocrine disruption in zebrafish larvae. Aquat Toxicol 110-111:141–148. CrossRefGoogle Scholar
  12. Christen V, Fent K (2014) Tissue-, sex- and development-specific transcription profiles of eight UDP-glucuronosyltransferase genes in zebrafish (Danio rerio) and their regulation by activator of aryl hydrocarbon receptor. Aquat Toxicol 150:93–102CrossRefGoogle Scholar
  13. Colli-Dula RC, Martyniuk CJ, Kroll KJ, Prucha MS, Kozuch M, Barber DS, Denslow ND (2014) Dietary exposure of 17-alpha ethinylestradiol modulates physiological endpoints and gene signaling pathways in female largemouth bass (Micropterus salmoides). Aquat Toxicol 156:148–160CrossRefGoogle Scholar
  14. Cosnefroy A, Brion F, Maillot-Maréchal E, Porcher JM, Pakdel F, Balaguer P, Aït-Aïssa S (2012) Selective activation of zebrafish estrogen receptor subtypes by chemicals by using stable reporter gene assay developed in a zebrafish liver cell line. Toxicol Sci 125:439–449CrossRefGoogle Scholar
  15. Cunha E, Santos MM, Moradas-Ferreira P, Ferreira M (2016) Simvastatin effects on detoxification mechanisms in Danio rerio embryos. Environ Sci Pollut Res 23:10615–10629CrossRefGoogle Scholar
  16. Ducharme NA, Peterson LE, Benfenati E, Reif D, McCollum CW, Gustafsson JA, Bondesson M (2013) Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies. Reprod Toxicol 41:98–108CrossRefGoogle Scholar
  17. Duong CN, Ra JS, Schlenk D, Kim SD, Choi HK, Kim SD (2010) Sorption of estrogens onto different fractions of sediment and its effect on vitellogenin expression in male Japanese medaka. Arch Environ Contam Toxicol 59:147–156CrossRefGoogle Scholar
  18. EC (2002) 4-Nonylphenol (branched) and nonylphenol. CAS Nos: 84852-15-3 and 25154-52-3. EINECS Nos: 284-325-5 and 246-672-0. Summ Risk Assess Report 1–32Google Scholar
  19. EC (2013) Directive 2013/39/EU of the European Parliament and of the Council of 12 August 2013, amending Directives 2000/60/EC and /105/EC as regards priority substances in the field of water policy. Off. J. Eur. Communities L 8, 24–226Google Scholar
  20. Environment Canada (2009) Canadian sediment quality guidelines for the protection of aquatic life: polychlorinated biphenyls (PCBs). Canadian Council of Ministers of the Environment, 1999, updated 2001, revised 2009Google Scholar
  21. Environment Canada (2013) Canadian Environmental Protection Act, 1999 – Federal Environmental Quality Guidelines Polybrominated Diphenyl Ethers (PBDEs), 25Google Scholar
  22. Escher BI, van Daele C, Dutt M, Tang JYM, Altenburger R (2013) Most oxidative stress response in water samples comes from unknown chemicals: the need for effect-based water quality trigger values. Environ Sci Technol 47:7002–7011CrossRefGoogle Scholar
  23. EU, European Union (2008a) Risk assessment report. 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl cyclopenta-γ-2-benzopyran(1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylin-deno[5,6-C]pyran - HHCB); CAS No: 1222-05-5; EINECS No: 214–946-9; Risk assessment Final Approved VersionGoogle Scholar
  24. EU, European Union (2008b) Risk assessment report. 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-napthyl)ethan-1-one (AHTN); CAS No: 1506-02-1 or 21145-77-7; EINECS No: 216-133-4 or 244-240-6; Risk assessment Final Approved VersionGoogle Scholar
  25. Fernández C, Carbonell G, Babín M (2015) Effects of individual and a mixture of pharmaceuticals and personal-care products on cytotoxicity, EROD activity and ROS production in a rainbow trout gonadal cell line (RTG-2). J Appl Toxicol 33:1203–1212Google Scholar
  26. Filby AL, Thorpe KL, Maack G, Tyler CR (2007) Gene expression profiles revealing the mechanisms of anti-androgen- and estrogen-induced feminization in fish. Aquat Toxicol 81:219–231CrossRefGoogle Scholar
  27. Garcia-Käufer M, Gartiser S, Hafner C, Schiwy S, Keiter S, Gründemann C, Hollert H (2015) Genotoxic and teratogenic effects of freshwater sediment samples from the Rhine and Elbe River (Germany) in zebrafish embryo using a multi-endpoint testing strategy. Environ Sci Poll Res 22:16341–16357CrossRefGoogle Scholar
  28. Glisic B, Hrubik J, Fa S, Dopudj N, Kovacevic R, Andric N (2016) Transcriptional profiles of glutathione-S-transferase isoforms, Cyp, and AOE genes in atrazine-exposed zebrafish embryos. Environ Toxicol 31:233–244. CrossRefGoogle Scholar
  29. Grund S, Higley E, Schönenberger R, Suter MJF, Giesy JP, Braunbeck T, Hecker M, Hollert H (2011) The endocrine disrupting potential of sediments from the Upper Danube River (Germany) as revealed by in vitro bioassays and chemical analysis. Environ Sci Pollut Res 18:446–460. CrossRefGoogle Scholar
  30. Guse B, Kail J, Radinger J, Schröder M, Kiesel J, Hering D, Wolter C, Fohrer N (2015) Eco-hydrologic model cascades: simulating land use and climate change impacts on hydrology, hydraulics and habitats for fish and macroinvertebrates. Sci Total Environ 533:542–556CrossRefGoogle Scholar
  31. Habibi HR, Nelson ER, Allan ERO (2012) New insights into thyroid hormone function and modulation of reproduction in goldfish. Gen Comp Endocrinol 175:19–26CrossRefGoogle Scholar
  32. Häfeli N, Schwartz P, Burkhardt-Holm P (2011) Embryotoxic and genotoxic potential of sewage system biofilm and river sediment in the catchment area of a sewage treatment plant in Switzerland. Ecotoxicol Environ Saf 74(5):1271–1279CrossRefGoogle Scholar
  33. Hallare AV, Kosmehl T, Schulze T, Hollert H, Köhler H-R, Triebskorn R (2005) Assessing contamination levels of Laguna Lake sediments (Philippines) using a contact assay with zebrafish (Danio rerio) embryos. Sci Total Environ 347:254–271CrossRefGoogle Scholar
  34. Hallare AV, Seiler TB, Hollert H (2011) The versatile, changing, and advancing roles of fish in sediment toxicity assessment—a review. J Soils Sediments 11:141–173. CrossRefGoogle Scholar
  35. Hallare AV, Morales ANY, Tanalgo BLAS, Rubio PYM, Macabeo APG (2016) Assessment of embryotoxicity of urban highway runoff in Manila using the zebrafish (Danio rerio) embryo toxicity (ZFET) test. Res J Pharm, Biol Chem Sci 7:43–51Google Scholar
  36. Hamers T, Kamstra JH, Cenijn PH, Pencikova K, Palkova L, Simeckova P, Vondracek J, Andersson PL, Stenberg M, Machala M (2011) In vitro toxicity profiling of ultrapure non-dioxin-like polychlorinated biphenyl congeners and their relative toxic contribution to PCB mixtures in humans. Toxicol Sci 121(1):88–100CrossRefGoogle Scholar
  37. Hanson AM, Kittilson JD, Martin LE, Sheridan MA (2014) Environmental estrogens inhibit growth of rainbow trout (Oncorhynchus mykiss) by modulating the growth hormone-insulin-like growth factor system. Gen Comp Endocrinol 196:130–138. CrossRefGoogle Scholar
  38. Hartnett L, Glynn C, Nolan CM, Grealy M, Byrnes L (2010) Insulin-like growth factor-2 regulates early neural and cardiovascular system development in zebrafish embryos. Int J Dev Biol 54:573–583CrossRefGoogle Scholar
  39. Hermsen SA, van den Brandhof EJ, van der Ven LT, Piersma AH (2011) Relative embryotoxicity of two classes of chemicals in a modified zebrafish embryotoxicity test and comparison with their in vivo potencies. Toxicol in Vitro 25:745–753CrossRefGoogle Scholar
  40. Hollert H, Dürr M, Erdinger L, Braunbeck T (2000) Cytotoxicity of settling particulate matter and sediments of the Neckar river (Germany) during a winter flood. Environ Toxicol Chem 19:528–534CrossRefGoogle Scholar
  41. Hollert H, Keiter S, König N, Rudolf M, Ulrich M, Braunbeck T (2003) A new sediment contact assay to assess particle-bound pollutants using zebrafish (Danio rerio) embryos. J Soils Sediments 3:197–207CrossRefGoogle Scholar
  42. Huang H, Wu Q (2010) Cloning and comparative analyses of the zebrafish Ugt repertoire reveal its evolutionary diversity. PLoS One 5(2):e9144CrossRefGoogle Scholar
  43. Huang GY, Liu YS, Chen XW, Liang YQ, Liu SS, Yang YY, Hu LX, Shi WJ, Tian F, Zhao JL, Chen J, Ying GG (2016) Feminization and masculinization of western mosquitofish (Gambusia affinis) observed in rivers impacted by municipal wastewaters. Sci Rep 6:20884. CrossRefGoogle Scholar
  44. ISO (1996) Water quality – determination of the acute lethal toxicity of substances to a freshwater fish (Brachydanio rerio Hamilton-Buchanan (Teleostei, Cyprinidae)) – part 3: flow-through method. EN ISO 7346-3. International Organization for Standardization, Geneva, SwitzerlandGoogle Scholar
  45. ISO (2004) Soil quality – determination of content of hydrocarbon in the range C10 to C40 by gas chromatography. ISO 16703:2004. International Organization for Standardization, Geneva, SwitzerlandGoogle Scholar
  46. Jia PP, Ma YB, Lu CJ, Mirza Z, Zhang W, Jia YF, Li WG, Pei DS (2016) The effects of disturbance on hypothalamus-pituitary-thyroid (HPT) axis in zebrafish larvae after exposure to DEHP. PLoS One 11(5):e0155762. CrossRefGoogle Scholar
  47. Jiang J, Wu S, Wang Y, An X, Cai L, Zhao X, Wu C (2015) Carbendazim has the potential to induce oxidative stress, apoptosis, immunotoxicity and endocrine disruption during zebrafish larvae development. Toxicol in Vitro 29:1473–1481CrossRefGoogle Scholar
  48. Jin Y, Zheng S, Pu Y, Shu L, Sun L, Liu W, Fu Z (2011) Cypermethrin has the potential to induce hepatic oxidative stress, DNA damage and apoptosis in adult zebrafish (Danio rerio). Chemosphere 82:398–404CrossRefGoogle Scholar
  49. Keiter S, Rastall A, Kosmehl T, Wurm K, Erdinger L, Braunbeck T, Hollert H (2006) Ecotoxicological assessment of sediment, suspended matter and water samples in the upper Danube River. A pilot study in search for the causes for the decline of fish catches. Environ Sci Pollut Res Int 13(5):308–319CrossRefGoogle Scholar
  50. Kienzler A, Bony S, Devaux A (2013) DNA repair activity in fish and interest in ecotoxicology: a review. Aquat Toxicol 134–135:47–56. CrossRefGoogle Scholar
  51. Kim S, Jung D, Kho Y, Choi K (2014) Effects of benzophenone-3 exposure on endocrine disruption and reproduction of Japanese medaka (Oryzias latipes) - a two generation exposure study. Aquat Toxicol 155:244–252CrossRefGoogle Scholar
  52. Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF (1995) Stages of embryonic development of the zebrafish. Dev Dyn 203:253–310CrossRefGoogle Scholar
  53. Kiparissis Y, Metcalfe TL, Balch GC, Metcalfe CD (2003) Effects of the antiandrogens, vinclozolin and cyproterone acetate on gonadal development in the Japanese medaka (Oryzias latipes). Aquat Toxicol 63:391–403. 00189-3
  54. Knecht AL, Goodal BC, Truong L, Simonich MT, Swanson AJ, Matzke MM, Anderson KA, Waters KM, Tanguay RL (2013) Comparative developmental toxicity of environmentally relevant oxygenated PAHs. Toxicol Appl Pharmacol 271:266–275CrossRefGoogle Scholar
  55. Kolpin DW, Blazer VS, Gray JL, Focazio MJ, Young JA, Alvarez DA, Iwanowicz LR, Foreman WT, Furlong ET, Speiran GK, Zaugg SD, Hubbard LE, Meyer MT, Sandstrom MW, Barber LB (2013) Chemical contaminants in water and sediment near fish nesting sites in the Potomac River basin: determining potential exposures to smallmouth bass (Micropterus dolomieu). Sci Total Environ 443:700–716CrossRefGoogle Scholar
  56. Kosmehl T, Krebs F, Manz W, Braunbeck T, Hollert H (2007) Differentiation between bioavailable and total hazard potential of sediment induced DNA fragmentation as measured by the comet assay with zebrafish embryos. J Soils Sediments 7(6):377–387CrossRefGoogle Scholar
  57. Le Fol V, Aït-Aïssa S, Cabaton N, Dolo L, Grimaldi M, Balaguer P, Perdu E, Debrauwer L, Brion F, Zalko D (2015) Cell-specific biotransformation of benzophenone-2 and bisphenol-S in zebrafish and human in vitro models used for toxicity and estrogenicity screening. Environ Sci Technol 49:3860–3868CrossRefGoogle Scholar
  58. Lee Pow CSD, Yost EE, Aday DD, Kullman SW (2016) Sharing roles: an assessment of Japanese Medaka estrogen receptors in vitellogenin induction. Environ Sci Technol 50:8886–8895CrossRefGoogle Scholar
  59. Li G, Xie P, Fu J, Hao L, Xiong Q, Li H (2008) Microcystin-induced variations in transcription of GSTs in an omnivorous freshwater fish, goldfish. Aquat Toxicol 88:75–80CrossRefGoogle Scholar
  60. Liu H, Gooneratne R, Huang X, Lai R, Wei J, Wang W (2015) A rapid in vivo zebrafish model to elucidate oxidative stress-mediated PCB126-induced apoptosis and developmental toxicity. Free Radic Biol Med 84:91–102CrossRefGoogle Scholar
  61. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2?ΔΔCT method. Methods 25(4):402–408CrossRefGoogle Scholar
  62. Macaulay LJ, Chen A, Rock KD, Dishaw LV, Dong W, Hinton DE, Stapleton HM (2015) Development toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptor β. Aquat Toxicol 168:38–47CrossRefGoogle Scholar
  63. MacDonald DD, Ingersoll CG, Berger TA (2000) Development and evaluation of consensus-based sediment quality guidelines for freshwater ecosystems. Arch Environ Contam Toxicol 39:20–31CrossRefGoogle Scholar
  64. Marlatt VL, Sun J, Curran CA, Bailey HC, Kennedy CK, Elphick JR, Martyniuk CJ (2014) Molecular responses to 17β-estradiol in early life stage salmonids. Gen Comp Endocrinol 203:203–214CrossRefGoogle Scholar
  65. Ming JH, Ye JY, Zhang YX, Xub P, Xie J (2015) Effects of dietary reduced glutathione on growth performance, non-specific immunity, antioxidant capacity and expression levels of IGF-I and HSP70 mRNA of grass carp (Ctenopharyngodon idella). Aquaculture 438:39–46CrossRefGoogle Scholar
  66. Montano M, Weiss J, Hoffmann L, Gutleb AC, Murk ATJ (2013) Metabolic activation of nonpolar sediment extracts results in enhanced thyroid hormone disrupting potency. Environ Sci Technol 47:8878–8886CrossRefGoogle Scholar
  67. Morcillo P, Esteban MA, Cuesta A (2016) Heavy metals produce toxicity, oxidative stress and apoptosis in the marine teleost fish SAF-1 cell line. Chemosphere 144:225–233CrossRefGoogle Scholar
  68. Mortensen AS, Arukwe A (2007) Interactions between estrogen- and Ah-receptor signaling pathways in primary culture of salmon hepatocytes exposed to nonylphenol and 3,3’,4,4’-tetrachlorobiphenyl (congener 77). Comp Hepatol 6:2. CrossRefGoogle Scholar
  69. Mortensen AS, Braathen M, Sandvik M, Arukwe A (2007) Effects of hydroxy-polychlorinated biphenyl (OH-PCB) congeners on the xenobiotic biotransformation gene expression patterns in primary culture of Atlantic salmon (Salmo salar) hepatocytes. Ecotoxicol Environ Safety 68:351–360CrossRefGoogle Scholar
  70. Moschet C, Wittmer I, Simovic J, Junghans M, Piazzoli A, Singer H, Stamm C, Leu C, Hollender J (2014) How a complete pesticide screening changes the assessment of surface water quality. Environ Sci Technol 48:5423–5432CrossRefGoogle Scholar
  71. Nagashima M, Fujikawa C, Mawatari K, Mori Y, Kato S (2011) HSP70, the earliest-induced gene in the zebrafish retina during optic nerve regeneration: its role in cell survival. Neurochem Int 58:888–895CrossRefGoogle Scholar
  72. Nagel R (2002) DarT: the embryo test with the zebrafish Danio rerio - a general model in ecotoxicology and toxicology. ALTEX 19(Suppl 1):38–48Google Scholar
  73. Nelson ER, Habibi HR (2013) Estrogen receptor function and regulation in fish and other vertebrates. Gen Comp Endocrinol 192:15–24. CrossRefGoogle Scholar
  74. Notch EG, Mayer GD (2009) Wastewater treatment effluent alters nucleotide excision repair in zebrafish ( Danio rerio). Comp Biochem Physiol Part C 150:307–313Google Scholar
  75. Nowell LH, Moran PW, Gilliom RJ, Calhoun DL, Ingersoll CG, Kemble NE, Kuivila KM, Phillips PJ (2013) Contaminants in stream sediments from seven United States metropolitan areas: part I: distribution in relation to urbanization. Arch Environ Contam Toxicol 64:32–51CrossRefGoogle Scholar
  76. OECD (2013) Test no. 210: fish, early-life stage toxicity test, OECD Publishing, Paris.
  77. Redelstein R, Zielke H, Spira D, Feiler U, Erdinger L, Zimmer H, Wiseman S, Hecker M, Giesy JP, Seiler TB, Hollert H (2015) Bioaccumulation and molecular effects of sediment-bound metals in zebrafish embryos. Environ Sci Pollut Res 22:16290–16304. CrossRefGoogle Scholar
  78. Regoli F, Giuliani ME (2014) Oxidative pathways of chemical toxicity and oxidative stress biomarkers in marine organisms. Mar Environ Res 93:106–117CrossRefGoogle Scholar
  79. Reindl KM, Sheridan MA (2012) Peripheral regulation of the growth hormone-insulin-like growth factor system in fish and other vertebrates. Comp Biochem Physiol A Mol Integr Physiol 163(3–4):231–245CrossRefGoogle Scholar
  80. Rombough PJ (2002) Gills are needed for ion-regulation before they are needed for O2 uptake in developing zebrafish, Danio rerio. J Exp Biol 205:1787–1794Google Scholar
  81. Roos WP, Kaina B (2013) DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett 332(2):237–248CrossRefGoogle Scholar
  82. Schiller V, Wichmann A, Kriehuber R, Schäfers C, Fischer R, Fenske M (2013) Transcriptome alterations in zebrafish embryos after exposure to environmental estrogens and anti-androgens can reveal endocrine disruption. Reprod Toxicol 42:210–223CrossRefGoogle Scholar
  83. Schulze T, Ulrich M, Maier D, Maier M, Terytze K, Braunbeck T, Hollert H (2015) Evaluation of the hazard potentials of river suspended particulate matter and floodplain soils in the Rhine basin using chemical analysis and in vitro bioassays. Environ Sci Pollut Res 22:14606–14620CrossRefGoogle Scholar
  84. Shao B, Zhu L, Dong M, Wang J, Wang J, Xie H, Zhang Q, Du Z (2012) DNA damage and oxidative stress induced by endosulfan exposure in zebrafish (Danio rerio). Ecotoxicology 21:1533–1540. CrossRefGoogle Scholar
  85. Sharma P, Tang S, Mayer GD, Patiño R (2016) Effects of thyroid endocrine manipulation on sex-related gene expression and population sex ratios in zebrafish. Gen Comp Endocrinol 235:38–47CrossRefGoogle Scholar
  86. Siegenthaler PF, Zhao Y, Zhang K, Fent K (2017) Reproductive and transcriptional effects of the antiandrogenic progestin chlormadinone acetate in zebrafish (Danio rerio). Environ Poll 223:346–356CrossRefGoogle Scholar
  87. Simpson SL, Batley GE, Chariton AA (2013) Revision of the ANZECC/ARMCANZ sediment quality guidelines. CSIRO land and water science report 08/07. CSIRO Land and Water, CanberraGoogle Scholar
  88. Soares J, Neuparth T, Lyssimachou A, Lima D, Santos MM (2017) 17α-ethynilestradiol and tributyltin mixtures modulates the expression of NER and p53 DNA repair pathways in male zebrafish gonads and disrupt offspring embryonic development. Ecological Indicators, in press, 2017.04.054
  89. Sonavane M, Creusot N, Maillot-Maréchal E, Péry A, Brion F, Aїt-Aïssa S (2016) Zebrafish-based reporter gene assays reveal different estrogenic activities in river waters compared to a conventional human-derived assay. Sci Total Environ 550:934–939CrossRefGoogle Scholar
  90. Sun L, Lin X, Jin R, Peng T, Peng Z, Fu Z (2014) Toxic effects of bisphenol A on early life stages of Japanese medaka (Oryzias latipes). Bull Environ Contam Toxicol 93:222–227CrossRefGoogle Scholar
  91. Takeuchi S, Iida M, Yabushita H, Matsuda T, Kojima H (2008) In vitro screening for aryl hydrocarbon receptor agonistic activity in 200 pesticides using a highly sensitive reporter cell line, DR-EcoScreen cells, and in vivo mouse liver cytochrome P450-1A induction by propanil, diuron and linuron. Chemosphere 74:155–165CrossRefGoogle Scholar
  92. Timme-Laragy AR, Van Tiem LA, Linney EA, Di Giulio RT (2009) Antioxidant responses and NRF2 in synergistic developmental toxicity of PAHs in zebrafish. Toxicol Sci 109(2):217–227CrossRefGoogle Scholar
  93. Urbatzka R, van Cauwenberge A, Maggioni S, Viganò L, Mandich A, Benfenati E, Lutz I, Kloas W (2007) Androgenic and antiandrogenic activities in water and sediment samples from the river Lambro, Italy, detected by yeast androgen screen and chemical analyses. Chemosphere 67:1080–1087CrossRefGoogle Scholar
  94. USEPA method 1668C (2010) Chlorinated biphenyl congeners in water, soil, sediment biosolids and tissue by HRGC/HRMS. Method 1668 Rev. C, US Environmental Protection Agency Office of Water Engineering and Analysis Division, EPA-820-R-10-005Google Scholar
  95. Vega-Morales T, Sosa-Ferrera Z, Santana-Rodríguez JJ (2013) Evaluation of the presence of endocrine-disrupting compounds in dissolved and solid wastewater treatment plant samples of Gran Canaria Island (Spain). BioMed Research International vol. 2013, Article ID 790570, 15 pages. CrossRefGoogle Scholar
  96. Viganò L, Arillo A, De Flora S, Lazorchak J (1995) Evaluation of microsomal and cytosolic biomarkers in a seven-day larval trout sediment toxicity test. Aquat Toxicol 31:189–202CrossRefGoogle Scholar
  97. Viganò L, Arillo A, Buffagni A, Camuso M, Ciannarella R, Crosa G, Falugi C, Galassi S, Guzzella L, Lopez A, Mingazzini M, Pagnotta R, Patrolecco L, Tartiri G, Valsecchi S (2003) Quality assessment of bed sediments of the River Po (Italy). Water Res 37:501–518CrossRefGoogle Scholar
  98. Viganò L, Mascolo G, Roscioli C (2015a) Emerging and priority contaminants with endocrine active potentials in sediments and fish from the River Po (Italy). Environ Sci Pollut Res 22:14050–14066. CrossRefGoogle Scholar
  99. Viganò L, De Flora S, Gobbi M, Guiso G, Izzotti A, Mandich A, Mascolo G, Roscioli C (2015b) Exposing native cyprinids (Barbus plebejus) juveniles to river sediments leads to gonadal alterations, genotoxic effects and thyroidal disruption. Aquat Toxicol 169:223–239CrossRefGoogle Scholar
  100. Viganò L, Loizeau JL, Mandich A, Mascolo G (2016) Medium- and long-term effects of estrogenic contaminants on the Middle River Po fish community as reconstructed from a sediment core. Arch Environ Contam Toxicol 71(4):454–472. CrossRefGoogle Scholar
  101. Wang Y, Zhang S (2011) Expression and regulation by thyroid hormone (TH) of zebrafish IGF-I gene and amphioxus IGFl gene with implication of the origin of TH/IGF signaling pathway. Comp Biochem Physiol A: Molecular & Integrative Physiology 160(4):474–479CrossRefGoogle Scholar
  102. Wang L, Ying GG, Zhao JL, Liu S, Yang B, Zhou LJ, Tao R, Su HC (2011) Assessing estrogenic activity in surface water and sediment of the Liao River system in northeast China using combined chemical and biological tools. Environ Poll 159:148–156CrossRefGoogle Scholar
  103. Weiss JM, Andersson PL, Zhang J, Simon E, Leonards PEG, Hamers T, Lamoree MH (2015) Tracing thyroid hormone disrupting compounds: database compilation and structure activity evaluation for an effect directed analysis of sediment. Anal Bioanal Chem 407:5625–5634CrossRefGoogle Scholar
  104. Wiebe JP, Beausoleil M, Zhang G, Cialacu V (2010) Opposing actions of the progesterone metabolites, 5α-dihydroprogesterone (5αP) and 3α-dihydroprogesterone (3αHP) on mitosis, apoptosis, and expression of Bcl-2, Bax and p21 in human breast cell lines. Journal of Steroid Biochemistry & Molecular Biology 118:125–132CrossRefGoogle Scholar
  105. Wu F, Fang Y, Li Y, Cui X, Zhang R, Guo G, Giesy JP (2014a) Predicted no-effect concentration and risk assessment for 17β-estradiol in waters of China. Rev Environ Contam Toxicol 228:31–56Google Scholar
  106. Wu F, Zheng Y, Gao J, Chen S, Wang Z (2014b) Induction of oxidative stress and the transcription of genes related to apoptosis in rare minnow (Gobiocypris rarus) larvae with Aroclor 1254 exposure. Ecotoxicol Environ Saf 110:254–260. CrossRefGoogle Scholar
  107. Wu M, Pan C, Chen Z, Jiang L, Lei P, Yang M (2017) Bioconcentration pattern and induced apoptosis of bisphenol A in zebrafish embryos at environmentally relevant concentrations. Environ Sci Poll Res 24:6611–6621. CrossRefGoogle Scholar
  108. Xing H, Li S, Wang X, Gao X, Xu S, Wang X (2013) Effects of atrazine and chlorpyrifos on the mRNA levels of HSP70 and HSC70 in the liver, brain, kidney and gill of common carp (Cyprinus carpio L.). Chemosphere 90:910–916CrossRefGoogle Scholar
  109. Yang J, Chan KM (2015) Evaluation of the toxic effects of brominated compounds (BDE-47, 99,209, TBPA) and bisphenol A (BPA) using a zebrafish liver cell line, ZFL. Aquat Toxicol 159:138–147CrossRefGoogle Scholar
  110. Zhang Y, Krysl RG, Ali JM, Snow DD, Bartelt-Hunt SL, Kolok AS (2015a) Impact of sediment on agrichemical fate and bioavailability to adult female fathead minnows: a field study. Environ Sci Technol 49:9037–9047CrossRefGoogle Scholar
  111. Zhang Y, Ding S, Bentsen CN, Ma S, Jia X, Meng W (2015b) Differences in stream fish assemblages subjected to different levels of anthropogenic pressure in the Taizi River catchment, China. Ichthyol Res 62(4):450–462CrossRefGoogle Scholar
  112. Zhang J, Li Y, Gupta AA, Nam K, Andersson PL (2016a) Identification and molecular interaction studies of thyroid hormone receptor disruptors among household dust contaminants. Chem Res in Toxicol 29:1345–1354CrossRefGoogle Scholar
  113. Zhang QF, Li YW, Liu ZH, Chen QL (2016b) Exposure to mercuric chloride induces developmental damage, oxidative stress and immunotoxicity in zebrafish embryos-larvae. Aquat Toxicol 181:76–85CrossRefGoogle Scholar
  114. Zheng JL, Yuan SS, Wu CW, Li WY (2016) Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish. Aquat Toxicol 177:261–268CrossRefGoogle Scholar
  115. Zheng X, Zhu Y, Liu C, Liu H, Giesy JP, Hecker M, Lam MHW, Yu H (2012) Accumulation and biotransformation of BDE-47 by zebrafish larvae and teratogenicity and expression of genes along the hypothalamus–pituitary–thyroid axis. Environ Sci Technol 46:12943–12951CrossRefGoogle Scholar
  116. Zhuang S, Lv X, Pan L, Lu L, Ge Z, Wang J, Wang J, Liu J, Liu W, Zhang C (2017) Benzotriazole UV 328 and UV-P showed distinct antiandrogenic activity upon human CYP3A4-mediated biotransformation. Environ Pollut 220:616–624. CrossRefGoogle Scholar
  117. Zucchi S, Mirbahai L, Castiglioni S, Fent K (2014) Transcriptional and physiological responses induced by binary mixtures of drospirenone and progesterone in zebrafish (Danio rerio). Environ Sci Technol 48:3523–3531CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Luigi Viganò
    • 1
    Email author
  • Nadia Casatta
    • 1
  • Anna Farkas
    • 2
  • Giuseppe Mascolo
    • 3
  • Claudio Roscioli
    • 1
  • Fabrizio Stefani
    • 1
  • Matteo Vitelli
    • 4
  • Fabio Olivo
    • 4
  • Laura Clerici
    • 4
  • Pasquale Robles
    • 4
  • Pierluisa Dellavedova
    • 4
  1. 1.CNR - National Research Council of Italy, IRSA - Water Research Institute BrugherioItaly
  2. 2.MTA Centre for Ecological Research, Balaton Limnological InstituteTihanyHungary
  3. 3.CNR - National Research Council of Italy, IRSA - Water Research InstituteBariItaly
  4. 4.ARPA – Regional Agency for Environmental Protection of Lombardy, Laboratories SectorMilanItaly

Personalised recommendations