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The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo). UVI3003 did not significantly activate human or mouse PPARγ in vitro; therefore, the activation of Xenopus PPARγ by UVI3003 is novel. The ability of UVI3003 to activate xPPARγ explains why UVI3003 and TPT yield similar phenotypes in Xenopus embryos. Our results indicate that activating PPARγ leads to teratogenic effects in Xenopus embryos. More generally, we infer that chemicals known to specifically modulate mammalian nuclear hormone receptors cannot be assumed to have the same activity in non-mammalian species, such as Xenopus. Rather they must be tested for activity and specificity on receptors of the species in question to avoid making inappropriate conclusions.
Alsop,
Constituents within pulp mill effluent deplete retinoid stores in white sucker and bind to rainbow trout retinoic acid receptors and retinoid X receptors.
2003, Pubmed
Alsop,
Constituents within pulp mill effluent deplete retinoid stores in white sucker and bind to rainbow trout retinoic acid receptors and retinoid X receptors.
2003,
Pubmed Barak,
PPAR gamma is required for placental, cardiac, and adipose tissue development.
1999,
Pubmed Blumberg,
Multiple retinoid-responsive receptors in a single cell: families of retinoid "X" receptors and retinoic acid receptors in the Xenopus egg.
1992,
Pubmed
,
Xenbase Chamorro-García,
Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor gamma-independent mechanism.
2012,
Pubmed Collins,
Teratology of retinoids.
1999,
Pubmed Dawson,
Synthetic retinoids and their nuclear receptors.
2004,
Pubmed Elmazar,
RARalpha-mediated teratogenicity in mice is potentiated by an RXR agonist and reduced by an RAR antagonist: dissection of retinoid receptor-induced pathways.
1997,
Pubmed Ferré,
The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity.
2004,
Pubmed Fort,
Enhancing the predictive validity of Frog Embryo Teratogenesis Assay--Xenopus (FETAX).
2002,
Pubmed
,
Xenbase Greene,
Isolation of the human peroxisome proliferator activated receptor gamma cDNA: expression in hematopoietic cells and chromosomal mapping.
1995,
Pubmed Grimaldi,
Reporter cell lines to evaluate the selectivity of chemicals for human and zebrafish estrogen and peroxysome proliferator activated γ receptors.
2015,
Pubmed Grün,
Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling.
2006,
Pubmed Grün,
Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates.
2006,
Pubmed
,
Xenbase Hashimoto,
Nuclear receptor antagonists designed based on the helix-folding inhibition hypothesis.
2005,
Pubmed Hu,
Use of the enhanced frog embryo teratogenesis assay-Xenopus (FETAX) to determine chemically-induced phenotypic effects.
2015,
Pubmed
,
Xenbase Hu,
An assay to determine the sensitive window of embryos to chemical exposure using Xenopus tropicalis.
2016,
Pubmed
,
Xenbase Inoue,
Screening of agonistic activities against four nuclear receptors in wastewater treatment plants in Japan using a yeast two-hybrid assay.
2011,
Pubmed Janesick,
Active repression by RARγ signaling is required for vertebrate axial elongation.
2014,
Pubmed
,
Xenbase Janesick,
RIPPLY3 is a retinoic acid-inducible repressor required for setting the borders of the pre-placodal ectoderm.
2012,
Pubmed
,
Xenbase Kanayama,
Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway.
2005,
Pubmed Kanayasu-Toyoda,
HX531, a retinoid X receptor antagonist, inhibited the 9-cis retinoic acid-induced binding with steroid receptor coactivator-1 as detected by surface plasmon resonance.
2005,
Pubmed Kastner,
Genetic analysis of RXR alpha developmental function: convergence of RXR and RAR signaling pathways in heart and eye morphogenesis.
1994,
Pubmed Kliewer,
Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.
1994,
Pubmed Kubota,
PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.
1999,
Pubmed Lehmann,
Retinoids selective for retinoid X receptor response pathways.
1992,
Pubmed Li,
A two-hybrid yeast assay to quantify the effects of xenobiotics on retinoid X receptor-mediated gene expression.
2008,
Pubmed Li,
The association between prenatal exposure to organochlorine pesticides and thyroid hormone levels in newborns in Yancheng, China.
2014,
Pubmed Lyssimachou,
The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.
2015,
Pubmed Mangelsdorf,
Retinoid receptors.
1993,
Pubmed Michalik,
PPAR expression and function during vertebrate development.
2002,
Pubmed
,
Xenbase Nahoum,
Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function.
2007,
Pubmed Nishikawa,
Involvement of the retinoid X receptor in the development of imposex caused by organotins in gastropods.
2004,
Pubmed Perlmann,
Two distinct dimerization interfaces differentially modulate target gene specificity of nuclear hormone receptors.
1996,
Pubmed Riu,
Halogenated bisphenol-A analogs act as obesogens in zebrafish larvae (Danio rerio).
2014,
Pubmed Rosen,
PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro.
1999,
Pubmed Rosen,
PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth.
2001,
Pubmed Sambrook,
Calcium-phosphate-mediated Transfection of Eukaryotic Cells with Plasmid DNAs.
2006,
Pubmed Tontonoz,
Fat and beyond: the diverse biology of PPARgamma.
2008,
Pubmed Turusov,
Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks.
2002,
Pubmed Willhite,
Receptor-selective retinoid agonists and teratogenic activity.
1996,
Pubmed Yu,
Teratogenic effects of triphenyltin on embryos of amphibian (Xenopus tropicalis): a phenotypic comparison with the retinoid X and retinoic acid receptor ligands.
2011,
Pubmed
,
Xenbase Yuan,
Stage-specific malformations and phenotypic changes induced in embryos of amphibian (Xenopus tropicalis) by triphenyltin.
2011,
Pubmed
,
Xenbase Zhen,
Identification of retinoic acid receptor agonists in sewage treatment plants.
2009,
Pubmed Zhu,
Effects of antagonist of retinoid X receptor (UVI3003) on morphology and gene profile of Xenopus tropicalis embryos.
2014,
Pubmed
,
Xenbase
