TY - JOUR
T1 - Effects of antagonist of retinoid X receptor (UVI3003) on morphology and gene profile of Xenopus tropicalis embryos
AU - Zhu, Jingmin
AU - Shi, Huahong
AU - Zhu, Pan
AU - Hu, Lingling
AU - Wu, Lijiao
AU - Yang, Yi
AU - Rotchell, Jeanette M.
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
KW - Amphibian
KW - Antagonist
KW - Retinoid X receptor
KW - Teratogenicity
KW - UVI3003
UR - https://www.scopus.com/pages/publications/84902524086
U2 - 10.1016/j.etap.2014.05.010
DO - 10.1016/j.etap.2014.05.010
M3 - 文章
C2 - 24950139
AN - SCOPUS:84902524086
SN - 1382-6689
VL - 38
SP - 153
EP - 162
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
IS - 1
ER -