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Imposex in marine gastropods may be caused by binding of organotins to retinoid X receptor

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Abstract

Organotin compounds have been widely used as antifouling paints for ships and fishing nets since the 1960s and have thus been released into marine environments. Aquatic invertebrates, particularly marine gastropods, are extremely sensitive to organotin compounds such as tributyltin (TBT) and triphenyltin (TPT) and undergo changes in sexual identity in response to exposure. This worldwide phenomenon is one of the worst consequences of pollution by man-made chemicals and has led to the ban of such compounds in antifouling paints in a number of countries, although organotin compounds still exist in the environment. So far, very low-concentrations of TBT or TPT have been shown to induce imposex (superimposition of male genitalia on female) in marine gastropods. Although the imposex induction mechanism has been controversial for many years, it was recently reported that TBT and TPT are potent and efficacious activators of retinoid X receptor (RXR), a member of the nuclear receptor superfamily. In this review, I discuss the involvement of RXR in the development of gastropod imposex.

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References

  • Agostini M, Fletterick RJ, Beck-Peccoz P, Reinhardt W, Binder G, Ranke MB, Hermus A, Hesch RD, Lazarus J, Newrick P, Parfitt V, Raggatt P, Zegher FD, Chatterjee VKK (1998) A role for helix 3 of the TRβ ligand-binding domain in coactivator recruitment identified by characterization of a third cluster of mutations in resistance to thyroid hormone. EMBO J 17:4760–4770

    Article  Google Scholar 

  • Axiak V, Vella AJ, Micaleff D, Chircop P, Mintoff B (1995) Imposex in Hexaplex trunculus (Gastropoda: Muricidae): first results from biomonitoring of tributyltin contamination in the Mediterranean. Mar Biol 121:685–691

    Article  Google Scholar 

  • Bettin C, Oehlmann J, Stroben E (1996) TBT-induced imposex in marine neo-gastropods is mediated by an increasing androgen level. Helgolander Meeresunters 50:299–317

    Article  Google Scholar 

  • Blair RM, Fang H, Branham WS, Hass BS, Dial SL, Moland CL, Tong W, Shi L, Perkins R, Sheehan DM (2000) The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci 54:138–153

    Article  CAS  Google Scholar 

  • Boehm MF, Zhang L, Zhi L, McClurg MR, Berger E, Wagoner M, Mais DE, Suto CM, Davies JA, Heyman RA (1995) Design and synthesis of potent retinoid X receptor selective ligands that induce apoptosis in leukemia cells. J Med Chem 38:3146–3155

    Article  CAS  Google Scholar 

  • Bourguet W, Ruff M, Chambon P, Gronemeyer H, Moras D (1995) Crystal structure of the ligand-binding domain of the human nuclear receptor RXR-alpha. Nature 375:377–382

    Article  CAS  Google Scholar 

  • Brzozowski AM, Pike ACW, Dauter Z, Hubbard RE, Bonn T, Engstrom L, Greene GL, Gustagsson JA, Carlquist M (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753–758

    Article  CAS  Google Scholar 

  • Bryan GW, Gibbs PE, Burt GR (1988) A comparison of the effectiveness of tri-n-butyltin chloride and five other organotin compounds in promoting the development of imposex in the dog-whelk, Nucella lapillus. J Mar Biol Assoc UK 68:733–744

    Article  CAS  Google Scholar 

  • Bryan GW, Gibbs PE, Burt GR, Hummerstone LG (1987) The effects of tributyltin (TBT) accumulation on adult dog-whelk, Nucella lapillus: long-term field and laboratory experiments. J Mar Biol Assoc UK 67:525–544

    Article  CAS  Google Scholar 

  • Bryan GW, Gibbs PE, Hummerstone LG, Burt GR (1986) The decline of the gastropod Nucella lapillus around the south-west of England: evidence for the effect of tributyltin from antifouling paints. J Mar Biol Assoc UK 66:611–640

    Article  CAS  Google Scholar 

  • Colborn T, Dumanoski D, Myers JP (1996) Our stolen future. Dutton, New York

    Google Scholar 

  • Cooke GM (2002) Effects of organotins on human aromatase activity in vitro. Toxicol Lett 126:121–130

    Article  CAS  Google Scholar 

  • Escriva H, Delaunay F, Laudet V (2000) Ligand binding and nuclear receptor evolution. BioEssays 22:717–727

    Article  CAS  Google Scholar 

  • Escriva H, Safi R, Hanni C, Langlois M-C, Saumitou-Laprade P, Sthehelin D, Capron A, Pierce R, Laudet V (1997) Ligand binding was acquired during evolution of nuclear receptors. Proc Natl Acad Sci USA 94:6803–6808

    Article  CAS  Google Scholar 

  • Fent K (1996) Ecotoxicology of organotin compounds. Crit Rev Toxicol 26:1–117

    Article  CAS  Google Scholar 

  • Féral C, Le Gall S (1983) The influence of a pollutant factor (tributyltin) on the neuroendocrine mechanism responsible for the occurrence of a penis in the females of Ocenebra erinacea. In: Lever J, Boer HH (eds) Molluscan neuro-endocrinology. North Holland Publ Co, Amsterdam, pp 173–175

    Google Scholar 

  • Gibbs PE, Bryan GW (1986) Reproductive failure in populations of the dog-whelk, Nucella lapillus, caused by imposex induced by tributyltin from antifouling paints. J Mar Biol Assoc UK 66:767–777

    Article  CAS  Google Scholar 

  • Gibbs PE, Bryan GW, Pascoe PL, Burt GR (1987) The use of the dog-whelk, Nucella lapillus, as an indicator of tributyltin (TBT) contamination. J Mar Biol Assoc UK 67:507–523

    Article  CAS  Google Scholar 

  • Giguére V (1999) Orphan nuclear receptors: from gene to function. Endocr Rev 20:689–725

    PubMed  Google Scholar 

  • Gray LE, Ostby J, Furr J, Wolf CJ, Lambright C, Parks L, Veeramachaneni DN, Wilson V, Price M, Hotchkiss A, Oriando E, Guillette L (2001) Effects of environmental antiandrogens on reproductive development in experimental animals. Hum Reprod Update 7:248–264

    Article  CAS  Google Scholar 

  • Heidrich DD, Steckelbroek S, Klingmuller D (2001) Inhibition of human cytochrome P450 aromatase activity by butyltins. Steroids 66:763–769

    Article  CAS  Google Scholar 

  • Henrich VC, Brown NE (1995) Insect nuclear receptors: a developmental and comparative perspective. Insect Biochem Mol Biol 25:881–897

    Article  CAS  Google Scholar 

  • Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C (1992) 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 68:397–406

    Article  CAS  Google Scholar 

  • Horiguchi T, Shiraishi H, Shimizu M, Morita M (1997a) Imposex in sea snails, caused by organotin (tributyltin and triphenyltin) pollution in Japan: a survey. Appl Organomet Chem 11:452–455

    Article  Google Scholar 

  • Horiguchi T, Shiraishi H, Shimizu M, Morita M (1997b) Effects of triphenyltin chloride and five other organotin compounds on the development of imposex in the rock shell, Thais clavigera. Environ Pollut 95:452–455

    Article  Google Scholar 

  • Horton C, Maden M (1995) Endogenous distribution of retinoids during normal development and teratogenesis in the mouse embryo. Dev Dyn 202:312–323

    Article  CAS  Google Scholar 

  • Kanayama T, Kobayashi N, Mamiya S, Nakanishi T, Nishikawa J (2005) Organotin compounds promote adipocyte differentiation as agonists of the peroxisome activated receptor (PPAR)γ/retinoid X receptor (RXR) pathway. Mol Pharmacol 67:766–774

    Article  CAS  Google Scholar 

  • Kanayama T, Mamiya S, Nishihara T, Nishikawa J (2003) Basis of a high-throughput method for nuclear receptor ligand. J Biochem 133:791–797

    Article  CAS  Google Scholar 

  • Kastner P, Grondona J, Mark M, Gansmuller A, LeMeur M, Decimo D, Vonesch JL, Dolle P, Chambon P (1994) Genetic analysis of RXRα developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis. Cell 78:987–1003

    Article  CAS  Google Scholar 

  • Kastner P, Mark M, Leid M, Gansmuller A, Chin W, Grondona JM, Decimo D, Krezel W, Dierich A, Chambon P (1996) Abnormal spermatogenesis in RXRβ mutant mice. Genes Dev 10:80–92

    Article  CAS  Google Scholar 

  • Kostrouch Z, Kostrouchova M, Love W, Jannini E, Piatigorsky J, Rall JE (1998) Retinoic acid X receptor in the diploblast, Tripedalia cystophora. Proc Natl Acad Sci USA 95:13442–13447

    Article  CAS  Google Scholar 

  • Krezel W, Dupe V, Mark M, Dierich A, Kastner P, Chambon P (1996) RXRγ null mice are apparently normal and compound RXRα+/−/RXRβ-/-/RXRγ-/- mutant mice are viable. Proc Natl Acad Sci USA 93:9010–9014

    Article  CAS  Google Scholar 

  • Laudet V (1997) Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor. J Mol Endocrinol 19:207–226

    Article  CAS  Google Scholar 

  • LeBlanc GA, Campbell PM, den Besten P, Brown RP, Chang ES, Coats JR, de Fur PL, Dhadialla T, Edwards J, Riddiford LM, Simpson MG, Snell TW, Thorndyke M, Matsumura F (1999) The endocrinology of invertebrates. In: deFur P, Crane M, Ingersoll C, Tattersfield L (eds) Endocrine disruption in invertebrates: endocrinology, testing and assessment. SETAC Press, Pensacola, FL, pp 23–106

    Google Scholar 

  • Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA (1995) An antidiabetic thiazolidinedione is a high-affinity ligand for peroxisome proliferator-activated recptor gamma. J Biol Chem 270:12953–12956

    Article  CAS  Google Scholar 

  • Maglich JM, Sluder A, Guan X, Shi Y, Mckee DD, Carrick K, Kamdar K, Wilson TM, Moore JT (2001) Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes. Genome Biol 2:1–7

    Article  Google Scholar 

  • Mangelsdorf DJ, Borgemeyer U, Heyman RA, Yang-Zhou J, Ong ES, Oro AE, Kakizuka A, Evans RM (1992) Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 6:329–344

    Article  CAS  Google Scholar 

  • Mangelsdorf DJ, Evans RM (1995) The RXR heterodimers and orphan receptors. Cell 83:841–850

    Article  CAS  Google Scholar 

  • Matthiessen P, Reynoldson T, Billinghurst Z, Brassard DW, Cameron P, Chandler GT, Davies IM, Horiguchi T, Mount DR, Oehlmann J, Pottinger TG, Sibley PK, Thompson HM, Vethaak AD (1999) Field assessment for endocrine disruption in invertebrates. In: deFur P, Crane M, Ingersoll C, Tattersfield L (eds) Endocrine disruption in invertebrates: endocrinology, testing and assessment. SETAC Press, Pensacola, FL, pp 199–270

    Google Scholar 

  • Mukherjee R, Davies PJA, Crombie DL, Bischoff ED, Cesario RM, Jow L, Hamann LG, Boehm MF, Mondon CE, Nadzan AM, Paterniti Jr JR, Heyman RA (1997) Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature 386:407–410

    Article  CAS  Google Scholar 

  • Nishihara T, Nishikawa J, Kanayama T, Dakeyama F, Saito K, Imagawa M, Takatori S, Kitagawa Y, Hori S, Utsumi H (2000) Estrogenic activities of 517 chemicals by yeast two-hybrid assay. J Health Sci 46:282–298

    Article  CAS  Google Scholar 

  • Nishikawa J, Mamiya S, Kanayama T, Nishikawa T, Shiraishi F, Horiguchi T (2004) Involvement of the retinoid X receptor in the development of imposex caused by organotins in gastropods. Environ Sci Technol 38:6271–6276

    Article  CAS  Google Scholar 

  • Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, Kurokawa R, Rosenfold MG, Willson TM, Glass CK, Milburn MV (1998) Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor γ. Nature 395:137–143

    Article  CAS  Google Scholar 

  • Oberdörster E, McClellan-Green P (2000) The neuropeptide APGWamide induces imposex in the mud snail, Ilyanassa obsoleta. Peptides 21:1323–1330

    Article  Google Scholar 

  • Oberdörster E, McClellan-Green P (2002) Mechanisms of imposex induction in the mud snail, Ilyanassa obsoleta: TBT as a neurotoxin and aromatase inhibitor. Mar Environ Res 54:715–718

    Article  Google Scholar 

  • Renaud JP, Rochel N, Ruff M, Vivat V, Chambon P, Gronemeyer H, Moras D (1995) Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid. Nature 378:681–689

    Article  CAS  Google Scholar 

  • Ronis MJJ, Mason AZ (1996) The metabolism of testosterone by the periwinkle (Littorina littorea) in vitro and in vivo: effects of tributyltin. Mar Environ Res 42:161–166

    Article  CAS  Google Scholar 

  • Saitoh M, Yanase T, Morinaga H, Tanabe M, Mu YM, Nishi Y, Nomura M, Okabe T, Goto K, Takayanagi R, Nawata H (2001) Tributyltin or triphenyltin inhibits aromatase activity in human granulosa-like tumor cell line KGN. Biochem Biophys Res Commun 289:198–204

    Article  CAS  Google Scholar 

  • Smith BS (1971) Sexuality in the American mud snail, Nassarius obsoletus Say. Proc Malacol Soc Lond 39:377–378

    Google Scholar 

  • Sohoni P, Sumpter JP (1998) Several environmental estrogens are also anti-androgens. J Endocrinol 158:327–339

    Article  CAS  Google Scholar 

  • Sucov HM, Dyson E, Gumeringer CL, Price J, Chien KR, Evans RM (1994) RXRα mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. Genes Dev 8:1007–1018

    Article  CAS  Google Scholar 

  • ten Hallers-Tjabbes CC, Kemp JF, Boon JP (1994) Imposex in whelks Buccinum undatum from the open North Sea: relation to shipping traffic intensities. Mar Pollut Bull 28:311–313

    Article  Google Scholar 

  • Terlizzi A, Delos AL, Garaventa F, Faimali M, Geraci S (2004) Limited effectiveness of marine protected areas: imposex in Hexaplex trunculus (Gastropoda, Muricidae) populations from Italian marine reserves. Mar Pollut Bull 48:188–192

    Article  CAS  Google Scholar 

  • Terlizzi A, Geraci S, Minganti V (1998) Tributyltin (TBT) pollution in the coastal waters of Italy as indicated by imposex in Hexaplex trunculus (Gastropoda, Muricidae). Mar Pollut Bull 36:749–752

    Article  CAS  Google Scholar 

  • Thornton JW, Need E, Crews D (2003) Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling. Science 301:1714–1717

    Article  CAS  Google Scholar 

  • Tontonoz P, Hu E, Spiegelman BM (1994) Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 79:1147–1156

    Article  CAS  Google Scholar 

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  1. Laboratory of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1–6 Yamada-oka, Suita, 565-0871, Osaka, Japan

    Jun-ichi Nishikawa

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  1. Jun-ichi Nishikawa
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Correspondence to Jun-ichi Nishikawa.

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Communicated by R. Cattaneo-Vietti, Genova

Physical and Chemical Impacts on Marine Organisms, a Bilateral Seminar Italy–Japan held in November 2004

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Nishikawa, Ji. Imposex in marine gastropods may be caused by binding of organotins to retinoid X receptor. Marine Biology 149, 117–124 (2006). https://doi.org/10.1007/s00227-005-0210-3

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