Effects of antagonist of retinoid X receptor (UVI3003) on morphology and gene profile of Xenopus tropicalis embryos

We exposed Xenopus tropicalis embryos to a selective antagonist of retinoid X receptor (UVI3003). UVI3003 induced multiple malformations at the concentrations of 200-1000 mu g/L after 48 h exposure. The most prominent malformations affected brains, eyes, cement gland and fins. UVI3003 also induced variable and divergent malformations at 250-1500 mu g/L after 0-24 and 24-48h exposure. Microarray analysis showed that seven genes (rps15, serp2, fmr1, cyp2e1, Irrc9, ugt1a6 and LOC100490188) were differentially regulated in all three treatment groups after 0-24h exposure. The most significantly affected pathway was galactose metabolism. In 24-48 h exposure groups, 18 genes were differentially regulated, mainly comprising components of the PPAR signaling pathway. These results suggested that UVI3003 is teratogenic in amphibian embryos. Differential gene expression suggests that galactose metabolism and PPAR signaling pathways may provide underlying mechanistic detail accounting for the observed malformations. (C) 2014 Elsevier B.V. All rights reserved.