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

• UVI3003 is a highly selective antagonist of retinoid X receptor (RXR).
• It induced multiple phenotypes of malformations in Xenopus tropicalis embryos.
• The teratogenicity was much different after 0–24 and 24–48 h exposures.
• Retinoic acid signal was not significantly affected by UVI3003.
• UVI3003 had stage-specific teratogenicity in amphibian 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 μg/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 μg/L after 0–24 and 24–48 h exposure. Microarray analysis showed that seven genes (rps15, serp2, fmr1, cyp2e1, lrrc9, ugtla6 and LOC100490188) were differentially regulated in all three treatment groups after 0–24 h 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.