Skip to main content
Springer Nature Link
Log in

Exposure to 9-cis retinoic acid induces penis and vas deferens development in the female rock shell, Thais clavigera

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

To clarify how tributyltin (TBT) and triphenyltin (TPT) interact with the retinoid X receptor (RXR) to induce growth of male sex organs in female gastropods, we treated female rock shells (Thais clavigera) with three different concentrations (0.1, 1, or 5 μg/g wet wt) of 9-cis-retinoic acid (9CRA) or with a single concentration (1 μg/g wet wt) of TBT, TPT, or fetal bovine serum (as a control). The effects of each treatment were measured as the incidence of imposex, the length of the penis-like structure, and the vas deferens sequence (VDS) index. 9CRA induced imposex in a dose-dependent manner; imposex incidence was significantly higher in the rock shells that received 1 (P < 0.05) or 5 μg (P < 0.001) 9CRA than in the controls. After 1 month, the rock shells treated with 5 μg 9CRA exhibited substantial growth of the penis-like structure that was not as evident in the other treated shells. The length of the structure differed between the 0.1- and 5-μg 9CRA treatment groups (P < 0.05) but not between the 1- and 5-μg 9CRA treatment groups (P > 0.05). Compared with the control, the VDS index increased significantly in the 1- (P < 0.05) and 5-μg (P < 0.001) 9CRA groups. The penis-like structures behind the right tentacle in female rock shells treated with 5 μg 9CRA were essentially the same as the penises and vasa deferentia of normal males and of TBT-treated or TPT-treated imposexed females. These results further support the hypothesis that imposex in gastropods could be mediated by RXR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

Abbreviations

9CRA:

9-cis-retinoic acid

RXR:

retinoid X receptor

TBT:

tributyltin

TPT:

triphenyltin

VDS:

vas deferens sequence

References

  • Berrodin TJ, Marks MS, Ozato K, Linney E, Lazar MA. Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein. Mol Endocrinol 1992;6:1468–78.

    Article  PubMed  CAS  Google Scholar 

  • Bettin C, Oehlmann J, Stroben E. TBT-induced imposex in marine neogastropods is mediated by an increasing androgen level. Helgol Meeresunters 1996;50:299–317.

    Article  Google Scholar 

  • Bouton D, Escriva H, de Mendonca RL, Glineur C, Bertin B, Noël C, Robinson-Rechavi M, de Groot A, Cornette J, Laudet V, Pierce RJ. A conserved retinoid X receptor (RXR) from the mollusk Biomphalaria glabrata transactivates transcription in the presence of retinoids. J Mol Endocrinol 2005;34:567–82.

    Article  PubMed  CAS  Google Scholar 

  • Bryan GW, Gibbs PE, Hummerstone LG, Burt GR. The decline of the gastropod Nucella lapillus around south-west England: evidence for the effect of tributyltin from antifouling paints. J Mar Biol Assoc UK 1986;66:611–40.

    CAS  Google Scholar 

  • Bryan GW, Gibbs PE, Burt GR, Hummerstone LG. The effects of tributyltin (TBT) accumulation on adult dog-whelk, Nucella lapillus: long-term field and laboratory experiments. J Mar Biol Assoc UK 1987;67:525–44.

    CAS  Google Scholar 

  • Bryan GW, Gibbs PE, Burt GR. 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 1988;68:733–44.

    Article  CAS  Google Scholar 

  • de Groot A, de Rosny E, Juillan-Binard C, Ferrer JL, Laudet V, Pierce RJ, et al. Crystal structure of a novel tetrameric complex of agonist-bound ligand-binding domain of Biomphalaria glabrata retinoid X receptor. J Mol Biol 2005;354:841–53.

    Article  PubMed  CAS  Google Scholar 

  • de Urquiza AM, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlmann T. Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 2000;290:2140–4.

    Article  PubMed  Google Scholar 

  • Devine C, Hinman VF, Degnan BM. Evolution and developmental expression of nuclear receptor genes in the ascidian Herdmania. Int J Biol 2002;46:687–92.

    CAS  Google Scholar 

  • Escriva H, Safi R, Hanni C, Langlois MC, Saumitou-Laprade P, Stehelin D, et al. Ligand binding was acquired during evolution of nuclear receptors. Proc Natl Acad Sci USA 1997;94:6803–8.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Féral C, Le Gall S. The influence of a pollutant factor (TBT) on the neurosecretory mechanism responsible for the occurrence of a penis in the females of Ocenebra erinacea. In: Lever J, Boer HH, editors. Molluscan neuro-endocrinology. Amsterdam: North-Holland Publishing; 1983. p. 173–5.

  • Fioroni P, Oehlmann J, Stroben E. The pseudohermaphroditism of prosobranch; morphological aspects. Zool Anz 1991;226:1–26.

    Google Scholar 

  • Freebern WJ, Osman A, Niles EG, Christen L, LoVerde PT. Identification of a cDNA encoding a retinoid X receptor homologue from Schistosoma mansoni. Evidence for a role in female-specific gene expression. J Biol Chem 1999;247:4577–85.

    Article  Google Scholar 

  • Gearing KL, Gottlicher M, Teboul M, Widmark E, Gustafsson JA. Interaction of the peroxisome-proliferator-activated receptor and retinoid X receptor. Proc Natl Acad Sci USA 1993;90:1440–4.

    Article  PubMed  CAS  Google Scholar 

  • Gibbs PE, Bryan GW. Reproductive failure in populations of the dog-whelk, Nucella lapillus, caused by imposex induced by tributyltin from antifouling paints. J Mar Biol Assoc UK 1986;66:767–77.

    CAS  Google Scholar 

  • Gibbs PE, Bryan GW, Pascoe PL, Burt GR. The use of the dog-whelk, Nucella lapillus, as an indicator of tributyltin (TBT) contamination. J Mar Biol Assoc UK 1987;67:507–23.

    Article  CAS  Google Scholar 

  • Gibbs PE, Pascoe PL, Burt GR. Sex change in the female dog-whelk, Nucella lapillus, induced by tributyltin from antifouling paints. J Mar Biol Assoc UK 1988;68:715–31.

    Article  Google Scholar 

  • Gibbs PE, Bryan GW, Pascoe PL, Burt GR. Reproductive abnormalities in female Ocenebra erinacea (Gastropoda) resulting from tributyltin-induced imposex. J Mar Biol Assoc UK 1990;70:639–56.

    Google Scholar 

  • Goldberg ED. TBT: an environmental dilemma. Environment 1986;28:17–20, 42–4.

    Google Scholar 

  • Golub M, Doherty J. Triphenyltin as a potential human endocrine disruptor. J Toxicol Environ Health B Crit Rev 2004;7:281–95.

    Article  PubMed  CAS  Google Scholar 

  • Gooding MP, LeBlanc GA. Biotransformation and disposition of testosterone in the eastern mud snail Ilyanassa obsoleta. Gen Comp Endocrinol 2001;122:172–80.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Horiguchi T. Masculinization of female gastropod molluscs induced by organotin compounds, focusing on mechanism of actions of tributyltin and triphenyltin for development of imposex. Environ Sci 2006;13:77–87.

    PubMed  CAS  Google Scholar 

  • Horiguchi T, Shiraishi H, Shimizu M, Morita M. Imposex and organotin compounds in Thais clavigera and T. bronni in Japan. J Mar Biol Assoc UK 1994;74:651–69.

    CAS  Google Scholar 

  • Horiguchi T, Shiraishi H, Shimizu M, Morita M. Effects of triphenyltin chloride and five other organotin compounds on the development of imposex in the rock shell, Thais clavigera. Environ Pollut 1997a;95:85–91.

    Article  CAS  Google Scholar 

  • Horiguchi T, Shiraishi H, Shimizu M, Morita M. Imposex in sea snails, caused by organotin (tributyltin and triphenyltin) pollution in Japan: a survey. Appl Organomet Chem 1997b;11:451–55.

    Article  CAS  Google Scholar 

  • Horiguchi T, Kojima M, Hamada F, Kajikawa A, Shiraishi H, Morita M, et al. Impact of tributyltin and triphenyltin on ivory shell (Babylonia japonica) populations. Environ Health Perspect 2006;114(Suppl 1):13–9.

    PubMed  Google Scholar 

  • Horiguchi T, Nishikawa T, Ohta Y, Shiraishi H, Morita M. Retinoid X receptor gene expression and protein content in tissues of the rock shell Thais clavigera. Aquat Toxicol 2007;84:379–88.

    Article  PubMed  CAS  Google Scholar 

  • Horton C, Maden M. Endogenous distribution of retinoids during normal development and teratogenesis in the mouse embryo. Dev Dyn 1995;202:312–23.

    PubMed  CAS  Google Scholar 

  • Iguchi T, Katsu Y, Horiguchi T, Watanabe H, Blumberg B, Ohta Y. Endocrine disrupting organotin compounds are potent inducers of imposex in gastropods and adipogenesis in vertebrates. Mol Cell Toxicol 2007;3:1–10.

    Google Scholar 

  • Kajiwara M, Kuraku S, Kurokawa T, Kato K, Toda S, Hirose H, et al. Tissue preferential expression of estrogen receptor gene in the marine snail, Thais clavigera. Gen Comp Endocrinol 2006;148:315–26.

    Article  PubMed  CAS  Google Scholar 

  • Kamimura M, Fujiwara S, Kawamura K, Yubisui T. Functional retinoid receptors in budding ascidians. Dev Growth Differ 2000;42:1–8.

    Article  PubMed  CAS  Google Scholar 

  • Kostrouch Z, Kostrouchova M, Love W, Jannini E, Piatigorsky J, Rall JE. Retinoic acid X receptor in the diploblast, Tripedalia cystophora. Proc Natl Acad Sci USA 1998;95:13442–7.

    Article  PubMed  CAS  Google Scholar 

  • Levin AA, Sturzenbecker LJ, Kazmer S, Bosakowski T, Huselton C, Allenby G, et al. 9-cis-Retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha. Nature 1992;355:359–61.

    Article  PubMed  CAS  Google Scholar 

  • Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, et al. Identification of a nuclear receptor for bile acids. Science 1999;284:1362–5.

    Article  PubMed  CAS  Google Scholar 

  • Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell 1995;83:841–50.

    Article  PubMed  CAS  Google Scholar 

  • Mangelsdorf DJ, Borgmeyer U, Heyman RA, Zhou JY, Ong ES, Oro AE, et al. Characterization of three RXR genes that mediate the action of 9-cis-retinoic acid. Genes Dev 1992;6:329–44.

    Article  PubMed  CAS  Google Scholar 

  • Matthiessen P, Gibbs PE. Critical appraisal of the evidence for tributyltin-mediated endocrine disruption in molluscs. Environ Toxicol Chem 1998;17:37–43.

    Article  CAS  Google Scholar 

  • Matthiessen P, Reynoldson T, Billinghurst Z, Brassard DW, Cameron P, Chandler GT, et al. Field assessment for endocrine disruption in invertebrates. In: de Fur PL, Ingersoll C, Tattersfield L, editors. Endocrine disruption in invertebrates: endocrinology, testing, and assessment. Pensacola, FL: SETAC; 1999. p. 199–270.

  • Morris-Kay GM. Retinoids in mammalian embryonic development. In: Sherbet GV, editor. Retinoids: their physiological function and therapeutic potential. Greenwich, CT: JAI; 1997. p. 79–93.

  • Nagatomo K, Fujiwara S. Expression of Raldh2, Cyp26 and Hox-1 in normal and retinoic acid-treated Ciona intestinalis embryos. Gene Expr Patterns 2003;3:273–7.

    Article  PubMed  CAS  Google Scholar 

  • Nagatomo K, Ishibashi T, Satou Y, Satoh N, Fujiwara S. Retinoic acid affects gene expression and morphogenesis without upregulating the retinoic acid receptor in the ascidian Ciona intestinalis. Mech Dev 2003;120:363–72.

    Article  PubMed  CAS  Google Scholar 

  • Nishikawa J, Mamiya S, Kanayama T, Nishikawa T, Shiraishi F, Horiguchi T. Involvement of the retinoid X receptor in the development of imposex caused by organotins in gastropods. Environ Sci Technol 2004;38:6271–6.

    Article  PubMed  CAS  Google Scholar 

  • Oberdörster E, McClellan-Green P. The neuropeptide APGWamide induces imposex in the mud snail, Ilyanassa obsoleta. Peptides 2000;21:1323–30.

    Article  PubMed  Google Scholar 

  • Redfern CPF. Molecular mechanisms of the retinoid function. In: Sherbet GV, editor. Retinoids: their physiological function and therapeutic potential. Greenwich, CT: JAI; 1997. p. 35–77.

  • Ronis MJJ, Mason AZ. The metabolism of testosterone by the periwinkle (Littorina littorea) in vitro and in vivo: effects of tributyltin. Mar Environ Res 1996;42:161–6.

    Article  CAS  Google Scholar 

  • Schrader M, Bendik I, Becker-Andre M, Carlberg C. Interaction between retinoic acid and vitamin D signaling pathways. J Biol Chem 1993;268:17830–6.

    PubMed  CAS  Google Scholar 

  • Smith BS. Sexuality in the American mud snail, Nassarius obsoletus Say. Proc Malacol Soc Lond 1971;39:377–8.

    Google Scholar 

  • Spooner N, Gibbs PE, Bryan GW, Goad LJ. The effect of tributyltin upon steroid titres in the female dogwhelk, Nucella lapillus, and the development of imposex. Mar Environ Res 1991;32:37–49.

    Article  CAS  Google Scholar 

  • Thornton JW, Need E, Crews D. Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling. Science 2003;301:1714–7.

    Article  PubMed  CAS  Google Scholar 

  • Waxman DJ. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 1999;369:11–23.

    Article  PubMed  CAS  Google Scholar 

  • Wiens M, Batel R, Korzhev M, Muller WE. Retinoid X receptor and retinoic acid response in the marine sponge Suberites domuncula. J Exp Biol 2003;206:3261–71.

    Article  PubMed  CAS  Google Scholar 

  • Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJ. LXR, a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev 1995;9:1033–45.

    Article  PubMed  CAS  Google Scholar 

  • Zhang XK, Hoffmann B, Tran PB, Graupner G, Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature 1992;355:441–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partly supported by grants from the Japanese Ministry of the Environment (to T.H.) and by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Scientific Research [B] no. 17380121).

Author information

Authors and Affiliations

  1. Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan

    Toshihiro Horiguchi, Tomohiro Nishikawa, Fujio Shiraishi, Hiroaki Shiraishi & Masatoshi Morita

  2. Department of Veterinary Science, Faculty of Agriculture, Tottori University, 4-101 Koyamacho-Minami, Tottori, Tottori, 680-8553, Japan

    Yasuhiko Ohta

  3. Department of Environmental Conservation, Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime, 790-8566, Japan

    Masatoshi Morita

Authors
  1. Toshihiro Horiguchi
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Yasuhiko Ohta
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Tomohiro Nishikawa
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Fujio Shiraishi
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Hiroaki Shiraishi
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Masatoshi Morita
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Toshihiro Horiguchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Horiguchi, T., Ohta, Y., Nishikawa, T. et al. Exposure to 9-cis retinoic acid induces penis and vas deferens development in the female rock shell, Thais clavigera . Cell Biol Toxicol 24, 553–562 (2008). https://doi.org/10.1007/s10565-007-9051-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-007-9051-9

Keywords