Teratogenic effects of triphenyltin on embryos of amphibian (Xenopus tropicalis): a phenotypic comparison with the retinoid X and retinoic acid receptor ligands

J Hazard Mater. 2011 Sep 15;192(3):1860-8. doi: 10.1016/j.jhazmat.2011.07.027. Epub 2011 Jul 18.

Abstract

Triphenyltin (TPT) has high binding affinity with the retinoid X receptor (RXR) in animals. The natural ligand of RXR, 9-cis-retinoic acid (RA), is known to induce featured malformations in vertebrate embryos by disrupting RA signal. Limited information is available on the TPT effects on amphibians. We exposed embryos of amphibian (Xenopus tropicalis) to TPT, 9-cis-RA, all-trans-RA (ligand of retinoic acid receptor, RAR), and LGD1069 (a selective ligand of RXR). The 72h LC50 of TPT was 5.25 μg Sn/L, and 72h EC50 was 0.96 μg Sn/L. TPT induced multiple malformations including enlarged proctodaeum and narrow fins. TPT at 5 μg Sn/L inhibited the differentiation of skins and muscles. The reduced brain, loss of external eyes and bent axis were observed in RXR and RAR ligands treatments. TPT and tributyltin (TBT) inhibited the mRNA expression of RXRα and increased that of TRβ. The phenotypes of malformations induced by TPT were similar to those by TBT and were much different from those by the RXR and RAR ligands. These results indicated that TPT was acute toxic and had high teratogenicity to amphibian embryos, and that TPT induced phenotypes of malformations. TPT and TBT might have a similar teratogenic mechanism, which seems not to be mainly mediated through RA signal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Nonmammalian / drug effects*
  • Immunohistochemistry / methods
  • Ligands
  • Microscopy / methods
  • Microscopy, Electron, Scanning / methods
  • Muscle, Skeletal / embryology
  • Organotin Compounds / chemistry*
  • Organotin Compounds / pharmacology
  • Phenotype
  • RNA, Messenger / metabolism
  • Receptors, Retinoic Acid / chemistry*
  • Receptors, Retinoic Acid / metabolism
  • Retinoids / chemistry*
  • Skin / embryology
  • Teratogens / pharmacology*
  • Xenopus / embryology*

Substances

  • Ligands
  • Organotin Compounds
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Retinoids
  • Teratogens
  • triphenyltin