title: Effects of antagonist of retinoid X receptor (UVI3003) on morphology and gene profile of Xenopus tropicalis embryos.
abstract: 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 0-24h 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.
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China.
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China. Electronic address: hhshi@des.ecnu.edu.cn.
authors.forename: Huahong
authors.initials: H
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China.
authors.forename: Lijiao
authors.initials: L
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China; School of Biological, Biomedical and Environmental Sciences, University of Hull, Cottingham Road, Hull HU6 7RX, United Kingdom.
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Rotchell
mesh_terms: D058500:Animal Fins / Q000002:abnormalities / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000187:drug effects; D003373:Coumaric Acids / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D005124:Eye Abnormalities / Q000139:chemically induced; D005690:Galactose / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D047488:Retinoid X Receptors / Q000037:antagonists & inhibitors*; D013723:Teratogens / Q000633:toxicity*; D013764:Tetrahydronaphthalenes / Q000633:toxicity*; D014981:Xenopus / Q000002:abnormalities*
chemical_list: D003373:Coumaric Acids; D047492:Peroxisome Proliferator-Activated Receptors; D047488:Retinoid X Receptors; D013723:Teratogens; D013764:Tetrahydronaphthalenes; C525131:UVI 3003; D005690:Galactose
keywords: Amphibian; Antagonist; Retinoid X receptor; Teratogenicity; UVI3003