Comparative Study Of Sensitive Period And Genomics Of Teratogenicity In Xenopus Tropicalis Embryos After Exposure To Triphenyltin And UVI3003

Triphenyltin (TPT) is an important organictin compound and shows strong teratogenic effects on amphibian embryos. Retinoid X receptor (RXR) is an important target for chemical pollutants and drugs. RXR inhibitors can lead to severe deformity on amphibian embryos. There is an urgent need to study the teratogenic effects and mechanism of organictin compounds and RXR inhibitors in amphibian embryos. In this paper, we comparatively studied the sensitive period and genomics of teratogenicity in Xenopus tropicalis embryos after exposure to triphenyltin and UVI3003.Firstly, X. tropicalis embryos were exposed to10μg Sn/L triphenyltin during different periods. Severe malformations were observed in the embryos during24-36h and36-48h. The most characteristic malformations were narrow and enlarged proctodaeums. Our results suggest that UVI3003, at-RA, HX531and Cu-induced teratogenicity were highly stage-specific. It is important and useful to take sensitivity of period into the study of teratogenic effects and mechanism assessment of contaminants.Secondly, X. tropicalis embryos were exposed to various TPT concentrations (2.5,5,7.5μg Sn/L) during24-48h periods. Meanwhile, microarray analysis was used to measure the response of transcriptome. There were59022unique gene probes that were differentially expressed, including485in low concentration-treated group,138in middle concentration-treated group and410in high concentration-treated group. The qPCR data are similar to the results presented in microarray. Gene ontology revealed that the different genes involved in signal transduction, oxidation-reduction process, chipmaker the perception of smell and transmembrane transport. The main influenced pathways were ABC transporters, metabolic pathways and Steroid biosynthesis.Thirdly, X. tropicalis embryos were exposed to various UVI3003concentrations (250,500,750μg/L) during24-48h. Meanwhile, microarray analysis was carried out. There were58861unique gene probes that were differentially expressed, including75in low concentration-treated group,1145in middle concentration-treated group and4658in high concentration-treated group. The qPCR data were similar to the results presented in microarray. Gene ontology revealed that genes involved in the molecular features, metabolism, and immune cell process. The main influenced pathways were arginine metabolism and proline metabolism, drug metabolism, retinol metabolism and steroid hormone biosynthesis.Finally, the results of microarray analysis between the two chemicals were compared. Their commom points included:(1) The teratogenic effects on X. tropicalis were similarly period-specific, and the main phenoytpes of malformations were narrow fins, followed by enlarged proctodaeums.(2) Both arlll and ei/3h were significantly up-regulated.(3) GO analysis indicated that the different genes involved in signal transduction, oxidation-reduction process.(4) The commom pathways were metabolism and biosynthesis. Our results suggest that the mechanism of TPT and UVI3003-induced teratogenicity might be similar to each other.To sum up, it is an effective method to combine the sensitive period and ecotoxicgenomics when we study the teratogenic effects of contaminatns and reveal their mechanisms. In addition, these results provide scientific evidences for the ecological risk assessment of contaminants.