title: Divergent teratogenicity of agonists of retinoid X receptors in embryos of zebrafish (Danio rerio).
abstract: Zebrafish (Danio rerio) embryos were comparably exposed to seven known agonists of retinoid X receptors (RXRs) including two endogenous compounds (9-cis-retinoic acid and docosahexaenoic acid), four man-made selective ligands (LGD1069, SR11237, fluorobexarotene and CD3254), and a biocide (triphenyltin). The dominant phenotypes of malformation were sharp mouths and small caudal fins in 1 mg/L SR11237-treated group after 5 days exposure. 9-cis-retinoic acid and LGD1069 induced multiple malformations including small eyes, bent notochords, reduced brain, enlarged proctodaems, absence of fins, short tails and edema after 5 days exposure. Fluorobexarotene and CD3254 induced similar phenotypes of malformations after 5 days exposure at low concentration (20 μg/L) to those after the 1st d exposure at high concentrations (50 and 100 μg/L). Triphenlytin induced multiple malformations including deformed eyes, bent notochords, bent tails, and edema in hearts after 5 days exposure at concentrations of 1-10 μg Sn/L. In contrast, no discernible malformations were observed in triphenlytin-treated groups after each separate day exposure. These agonists not only showed different ability of teratogenicity but also induced different phenotypes of malformation in zebrafish embryos. In addition, the sensitive stages of zebrafish embryos were different in response to these agonists. Therefore, our results suggest that the agonists of RXRs had divergent teratogenicity in zebrafish embryos.
authors.affiliation: State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China. hhshi@des.ecnu.edu.cn
authors.forename: Huahong
authors.initials: H
authors.lastname: Shi
authors.forename: Pan
authors.initials: P
authors.lastname: Zhu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Sun
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D008297:Male; D009947:Organotin Compounds / Q000633:toxicity; D010641:Phenotype; D047488:Retinoid X Receptors / Q000819:agonists*; D013723:Teratogens / Q000032:analysis / Q000633:toxicity*; D014212:Tretinoin / Q000031:analogs & derivatives / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000254:growth & development*
chemical_list: D009947:Organotin Compounds; D047488:Retinoid X Receptors; D013723:Teratogens; D014874:Water Pollutants, Chemical; C105492:9,13-retinoic acid; D014212:Tretinoin; C030665:triphenyltin