Teratogenic Effects And Mechanism Of Triphenyltin On Embryos Of Xenopus Tropicalis

Amphibian populations have dramaticly declined globally over the past decades, and chemical pollution is regarded as one of the main causes. Triphenyltin (TPT) has been widely used as a biocide in agriculture and antifouling paints, proved to be an endocrine disruptor. However, toxicity of TPT on amphibians is poorly reported. In this study, embryos of Xenopus tropicalis were exposed to TPT to determine the teratogenic effects and mechanism of TPT.Firstly, X. tropicalis embryos were exposed to various TPT concentrations from blastula stages for24,48, and72h. After72h exposure, TPT decreased the percent of survival of embryos by34%and significantly reduced the whole body length in5μgSn/L treatment group. The72hLC50of TPT was5.25μgSn/L, and72hEC50was0.96μgSn/L.5μgSn/L TPT induced multiple malformations which were highly identical to those induced by TBT after48h exposure. The most obvious alterations were enlarged proctodaeum, narrow fin and skin hypopigmentation. TPT could also inhibited the differentiation of skins and muscles and significantly induce apoptosis in X. tropicalis embryos.Secondly, X. tropicalis embryos were also exposed to RXR/RAR ligands to reveal the teratogenic mechanism of TPT. Meanwhile, RT-PCR was used to analyze mRNA expression of RA related signal genes and TR genes, both in RAs and organotin treatment groups. The reduced brain, loss of external eyes and bent axis were observed in RXR and RAR ligand treatment groups. TPT and TBT inhibited the mRNA expression of RXRa and increased that of TRβ. TPT and TBT might induce teratogenicity ofXenoups embryos through the thyroid hormone (TH) signal pathway.Finally, X. tropicalis embryos were exposed to the binary mixtures of5μgSn/L and different concentrations of retinoic acids (all-trans RA and9-cis RA). Some new phenotypes of malformations were induced in binary exposure group, including extruded yolk and extrusion of notochord in the posterior tails, which have not been found in single exposure group.Our results suggest that TPT can inhibit the growth of X.troplicalis embryos and show strong teratogenic effects on them. Phenotypic and gene expression comparison indicates that TPT might share the same mechanism to result in malformations in X. tropicalis embryos as TBT, and this mechanism might not be mainly mediated through the RA signaling pathway.