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An Emerging Water Contaminant, Semicarbazide, Exerts an Anti-estrogenic Effect in Zebrafish (Danio rerio)

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Abstract

To determine the endocrine disrupting effect of semicarbazide, an emerging water contaminant, the changes in transcript levels of hepatic estrogen-response genes including vitellogenin-1 (vtg-1), estrogen receptor α (ERα), and estrogen receptor β (ERβ) were measured in male and female zebrafish exposed to semicarbazide with or without exogenous 17β-estradiol (E2). Exposure of male zebrafish to semicarbazide for 96 h or 28 days resulted in no significant induction in hepatic vtg-1, ERα, or ERβ mRNA expression, indicating that semicarbazide has no estrogenic effect. However, a remarkable anti-estrogenic effect of semicarbazide was demonstrated: semicarbazide treatment of female zebrafish for 96 h and 28 days resulted in significant decreases in transcript levels of vtg-1, ERα, and ERβ, as well as decreases in the gonadosomatic index level after 28 days. Moreover, semicarbazide exposure significantly inhibited the induction of vtg-1, ERα and ERβ mRNA by E2 when male zebrafish were co-exposed for 28 days.

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References

  • Commission E (2003) Commission Decision 2003/181/EC of 13 March 2003 amending Decision 2002/657/EC as regards the setting of minimum required performance limits (MRPLs) for certain residues in food of animal origin. Off J Eur Commun L 71

  • Cooper KM, Samsonova JV, Plumpton L, Elliott CT, Kennedy DG (2007) Enzyme immunoassay for semicarbazide—the nitrofuran metabolite and food contaminant. Anal Chim Acta 592:64–71

    Article  CAS  Google Scholar 

  • Davies TS, Lynch BS, Monro AM, Munro IC, Nestmann ER (2000) Rodent carcinogenicity tests need be no longer than 18 months: an analysis based on 210 chemicals in the IARC monographs. Food Chem Toxicol 38:219–235

    Article  CAS  Google Scholar 

  • Davis L, Katsu Y, Iguchi T, Lerner D, Hirano T, Grau E (2010) Transcriptional activity and biological effects of mammalian estrogen receptor ligands on three hepatic estrogen receptors in Mozambique tilapia. J Steroid Biochem Mol Biol 122(4):272–278

    Article  CAS  Google Scholar 

  • EFSA (2003a) Statement of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food Updating the Advice Available on Semicarbazide in Packaged Foods (Adopted 1.10.2003)

  • EFSA (2003b) Additional advice on semicarbazide, in particular related to baby food. Ad Hoc Expert Group Meeting, 9th October 2003. EFSA/AFC/ad hoc semicarbazide/2-final

  • Hoenicke K, Gatermann R, Hartig L, Mandix M, Otte S (2004) Formation of semicarbazide (semicarbazide) in food by hypochlorite treatment: is semicarbazide a specific marker for nitrofurazone abuse? Food Addit Contam 21(6):526–537

    Article  CAS  Google Scholar 

  • Hoffmann F, Kloas W (2012) The antiestrogens tamoxifen and fulvestrant abolish estrogenic impacts of 17α-ethinylestradiol on male calling behavior of xenopus laevis. PLoS ONE 7(9):e44715

    Article  CAS  Google Scholar 

  • Jordan V, Dix C, Rowsby L, Prestwich G (1977) Studies on the mechanism of action of the nonsteroidal antioestrogen tamoxifen (ICI 46,474) in the rat. Mol Cell Endocrinol 7(2):177–192

    Article  CAS  Google Scholar 

  • Katsu Y, Bermudez DS, Braun EL, Helbing C, Miyagawa S, Gunderson MP, Kohno S, Bryan TA, Guillette LJ Jr, Iguchi T (2004) Molecular cloning of the estrogen and progesterone receptors of the American alligator. Gen Comp Endocrinol 136(1):122–133

    Article  CAS  Google Scholar 

  • Kloas W, Urbatzka R, Opitz R, Würtz S, Behrends T, Hermelink B, Hofmann F, Jagnytsch O, Kroupova H, Lorenz C (2009) Endocrine disruption in aquatic vertebrates. Ann N Y Acad Sci 1163(1):187–200

    Article  CAS  Google Scholar 

  • Kristensen T, Edwards T, Kohno S, Baatrup E, Guillette L Jr (2007) Fecundity, 17β-estradiol concentrations and expression of vitellogenin and estrogen receptor genes throughout the ovarian cycle in female Eastern mosquito fish from three lakes in Florida. Aquat Toxicol 81(3):245–255

    Article  CAS  Google Scholar 

  • Lazier C, MacKay M (1993) Vitellogenin gene expression in teleost fish. In: Hochachka PW, Mommsen TP (Eds) Biochemistry and Molecular Biology of Fishes, 2, pp 391–405

  • Lim E, Ding J, Lam T (1991) Estradiol-induced vitellogenin gene expression in a teleost fish, oreochromis aureus. Gen Comp Endocrinol 82(2):206–214

    Article  CAS  Google Scholar 

  • Long X, Nephew KP (2006) Fulvestrant (ICI 182,780)-dependent interacting proteins mediate immobilization and degradation of estrogen receptor-α. J Biol Chem 281(14):9607–9615

    Article  CAS  Google Scholar 

  • Maranghi F, Tassinari R, Lagatta V, Moracci G, Macrì C, Eusepi A, Di Virgilio A, Scattoni M, Calamandrei G (2009) Effects of the food contaminant semicarbazide following oral administration in juvenile Sprague-Dawley rats. Food Chem Toxicol 47(2):472–479

    Article  CAS  Google Scholar 

  • Maranghi F, Tassinari R, Marcoccia D, Altieri I, Catone T, De Angelis G, Testai E, Mastrangelo S, Evandri MG, Bolle P (2010) The food contaminant semicarbazide acts as an endocrine disrupter: evidence from an integrated in vivo in vitro approach. Chem Biol Interact 183(1):40–48

    Article  CAS  Google Scholar 

  • Marlatt VL, Lakoff J, Crump K, Martyniuk CJ, Watt J, Jewell L, Atkinson S, Blais JM, Sherry J, Moon TW (2010) Sex-and tissue-specific effects of waterborne estrogen on estrogen receptor subtypes and E2-mediated gene expression in the reproductive axis of goldfish. Comput Biochem Physiol A 156(1):92–101

    Article  Google Scholar 

  • Ng TB, Idler DR (1983) Yolk formation and differentiation in teleost fishes. In: Hoar WS, Randall DJ, Donaldson EM (eds) Fish physiology, vol IXA. Academic Press, New York, pp 373–404

    Google Scholar 

  • Osborne CK, Elledge RM, Fuqua SA (1996) Estrogen receptors in breast cancer therapy. Sci Am 3:32–41

    CAS  Google Scholar 

  • Palstra AP, Schnabel D, Nieveen MC, Spaink HP, van den Thillart GE (2010) Temporal expression of hepatic estrogen receptor 1, vitellogenin1 and vitellogenin 2 in European silver eels. Gen Comp Endocrinol 166(1):1–11

    Article  CAS  Google Scholar 

  • Pereira A, Donato J, De Nucci G (2004) Implications of the use of semicarbazide as a metabolic target of nitrofurazone contamination in coated products. Food Addit Contam 21(1):63–69

    Article  CAS  Google Scholar 

  • Philips A, Chalbos D, Rochefort H (1993) Estradiol increases and anti-estrogens antagonize the growth factor-induced activator protein-1 activity in MCF-7 breast cancer cells without affecting c-fos and c-jun synthesis. J Biol Chem 268(19):14103–14108

    CAS  Google Scholar 

  • Richard A, Dixona RA, Daneel F (2002) Genistein. Phytochemistry 60(3):205–211

    Article  Google Scholar 

  • Rose J, Holbech H, Lindholst C, Nørum U, Povlsen A, Korsgaard B, Bjerregaard P (2002) Vitellogenin induction by 17β-estradiol and 17α-ethinylestradiol in male zebrafish (Danio rerio). Comput Biochem Physiol C 131(4):531–539

    Google Scholar 

  • Segner H (2009) Zebrafish (Danio rerio) as a model organism for investigating endocrine disruption. Comput Biochem Physiol C 149(2):187–195

    Google Scholar 

  • Sohoni P, Tyler C, Hurd K, Caunter J, Hetheridge M, Williams T, Woods C, Evans M, Toy R, Gargas M (2001) Reproductive effects of long-term exposure to bisphenol A in the fathead minnow (Pimephales promelas). Environ Sci Technol 35(14):2917–2925

    Article  CAS  Google Scholar 

  • Sun L, Wen L, Shao X, Qian H, Jin Y, Liu W, Fu Z (2010) Screening of chemicals with anti-estrogenic activity using in vitro and in vivo vitellogenin induction responses in zebrafish (Danio rerio). Chemosphere 78(7):793–799

    Article  CAS  Google Scholar 

  • Sun L, Shao X, Hu X, Chi J, Jin Y, Ye W, Fu Z (2011) Transcriptional responses in Japanese medaka (Oryzias latipes) exposed to binary mixtures of an estrogen and anti-estrogens. Aquat Toxicol 105(3):629–639

    Article  CAS  Google Scholar 

  • Toth B, Shimizu H, Erickson J (1975) Carbamylhydrazine hydrochloride as a lung and blood vessel tumour inducer in Swiss mice. Eur J Cancer 11(1):17–22

    Article  CAS  Google Scholar 

  • USEPA (1996) Ecological Effects Test Guidelines: OPPTS 850.1075 Fish Acute Toxicity Test, Freshwater and Marine. EPA 712-C-96-118, April 1996. Washington, DC: U.S. Environmental Protection Agency

  • USEPA (2004) http://www.epa.gov/dfe/pubs/flameret/altrep-v1/altrep-v1a-app-b.pdf (Updated September 2004)

  • Wahli W (1988) Evolution and expression of vitellogenin genes. Trends Genet 4(8):227–232

    Article  CAS  Google Scholar 

  • Wallace RA (1985) Vitellogenesis and oocyte growth in nonmammalian vertebrates. In: Browder LW (ed) Developmental biology, vol 1. Plenum, New York, pp 127–177

    Google Scholar 

  • Wang H, Tan JT, Emelyanov A, Korzh V, Gong Z (2005) Hepatic and extrahepatic expression of vitellogenin genes in the zebrafish, Danio rerio. Gene 356:91–100

    Article  CAS  Google Scholar 

  • Xu YJ, Sun YZ, Song XK, Tian X, Gong XH, Zhang XZ, Zhang LM (2010) Survey of semicarbazide contamination in coastal waters adjacent to the chaohe river estuary. Oceanologia Et Limnologia Sinica 41(4):1–5

    CAS  Google Scholar 

  • Yan Z, Lu G, He J (2012) Reciprocal inhibiting interactive mechanism between the estrogen receptor and aryl hydrocarbon receptor signaling pathways in goldfish (Carassius auratus) exposed to 17β-estradiol and benzo[a]pyrene. Comput Biochem Physiol C 156(1):17–23

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China [31170322].

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Authors and Affiliations

  1. Marine Life Science College, Ocean University of China, 5 Yushan Road, Qingdao, 266003, Shandong, People’s Republic of China

    Su Gao, Wei Wang, Hua Tian, Xiaona Zhang, Linlin Guo & Shaoguo Ru

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  1. Su Gao
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  2. Wei Wang
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  3. Hua Tian
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  4. Xiaona Zhang
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  5. Linlin Guo
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Correspondence to Wei Wang.

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Gao, S., Wang, W., Tian, H. et al. An Emerging Water Contaminant, Semicarbazide, Exerts an Anti-estrogenic Effect in Zebrafish (Danio rerio). Bull Environ Contam Toxicol 93, 280–288 (2014). https://doi.org/10.1007/s00128-014-1305-7

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  • DOI: https://doi.org/10.1007/s00128-014-1305-7

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