Teratogenic effects of triphenyltin on embryos of amphibian (Xenopus tropicalis): A phenotypic comparison with the retinoid X and retinoic acid receptor ligands

Lin, Yu; Zhang, Xiaoli; Yuan, Jing; Cao, Qinzhen; Liu, Junqi; Zhu, Ping; Shi, Huahong

doi:10.1016/j.jhazmat.2011.07.027

Cited by 38 publications

(18 citation statements)

References 33 publications

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“…In the present paper, we employed a modified frog embryo teratogenesis assay Xenopus (FETAX) protocol (Fort and Paul, 2002; Yu et al, 2011) to assess UVI3003-induced malformations in X. tropicalis embryos specific to certain developmental windows of chemical exposure. In a previous study, we found that the well-known agonist of RXR, triphenyltin (TPT), induced stage-specific malformations and phenotypic changes in Xenopus embryos (Yuan et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Xenopus tropicalis adults were obtained from Nasco (Fort Atkinson, WI, USA) and maintained according to previous methods (Yu et al, 2011). Breeding was induced by subcutaneous injection of human chorionic gonadotrophin (hCG) (Zhejiang, China) as described (Yu et al, 2011; Hu et al, 2015a).…”

Section: Methodsmentioning

confidence: 99%

“…Breeding was induced by subcutaneous injection of human chorionic gonadotrophin (hCG) (Zhejiang, China) as described (Yu et al, 2011; Hu et al, 2015a). The exposure experiments were conducted following the Frog Embryo Teratogenesis Assay (FETAX) protocol (Fort and Paul, 2002) with some modifications.…”

Section: Methodsmentioning

confidence: 99%

“…Primers were designed using Primer 3 and NCBI Primer-BLAST (Supplementary Table 1). Real-time quantitative PCR was performed according to our previous method (Yu et al, 2011). For each target mRNA, melting curves and gel electrophoresis verified the specificity of the amplified products and absence of primer dimers.…”

Section: Methodsmentioning

confidence: 99%

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The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

Zhu

Janesick

et al. 2017

Toxicology and Applied Pharmacology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

Zhu

Janesick

et al. 2017

Toxicology and Applied Pharmacology

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“…TBT at nanomolar levels has the ability to bind with higher affinity than the intrinsic ligands and these genomic transcriptional activations have been reported to mediate neurodevelopmental defects in Xenopus (Yu et al, 2011). In contrast, TBT elicits non-genomic pathway in mature rat neurons and brain tissues at nearly micromolar levels.…”

Section: Introductionmentioning

confidence: 99%

Tributyltin induces G2/M cell cycle arrest via NAD<sup>+</sup>-dependent isocitrate dehydrogenase in human embryonic carcinoma cells

et al. 2016

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-Organotin compounds, such as tributyltin (TBT), are well-known endocrine-disrupting chemicals (EDCs). We have recently reported that TBT induces growth arrest in the human embryonic carcinoma cell line NT2/D1 at nanomolar levels by inhibiting NAD + -dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the irreversible conversion of isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we examined whether TBT at nanomolar levels affects cell cycle progression in NT2/D1 cells. Propidium iodide staining revealed that TBT reduced the ratio of cells in the G1 phase and increased the ratio of cells in the G2/M phase. TBT also reduced cell division cycle 25C (cdc25C) and cyclin B1, which are key regulators of G2/M progression. Furthermore, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. The G2/M arrest induced by TBT was abolished by NAD-IDHα knockdown. Treatment with a cellpermeable α-ketoglutarate analogue recovered the effect of TBT, suggesting the involvement of NAD-IDH. Taken together, our data suggest that TBT at nanomolar levels induced G2/M cell cycle arrest via NAD-IDH in NT2/D1 cells. Thus, cell cycle analysis in embryonic cells could be used to assess cytotoxicity associated with nanomolar level exposure of EDCs.

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A representative retinoid X receptor antagonist UVI3003 induced teratogenesis in zebrafish embryos

Zheng

et al. 2014

J of Applied Toxicology

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Retinoid X receptor (RXR) interfering activity has been detected in different water resources. To study RXR disruptor-induced toxicological effects on vertebrates, embryos of zebrafish (Danio rerio) were exposed to a representative RXR antagonist UVI3003. Results showed that the teratogenic index (LC50 /EC50 ) of UVI3003 was as high as 5.4. UVI3003 induced multiple malformations of embryos, including deformed fins, reduced brains, small jaws, bent tails and edema in hearts, the degree of which became more severe with increasing exposure concentration. Although no significant difference was observed in the hatching rates between the exposure group and control, the whole body length was significantly reduced by 6.5% and 8.9% when exposed to 200 and 300 µg l(-1) of UVI3003, respectively. The heart rate also significantly decreased by 8.8-50.2% during exposure. Further experiments revealed that the pharyngula stage was the most sensitive development phase in terms of embryo response to UVI3003. The results demonstrated severe teratogenicity of RXR antagonist in zebrafish embryos and provided important data for ecotoxicological evaluation of RXR antagonists.

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Teratogenic effects of triphenyltin on embryos of amphibian (Xenopus tropicalis): A phenotypic comparison with the retinoid X and retinoic acid receptor ligands

Cited by 38 publications

References 33 publications

The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

The unexpected teratogenicity of RXR antagonist UVI3003 via activation of PPARγ in Xenopus tropicalis

Tributyltin induces G2/M cell cycle arrest via NAD<sup>+</sup>-dependent isocitrate dehydrogenase in human embryonic carcinoma cells

A representative retinoid X receptor antagonist UVI3003 induced teratogenesis in zebrafish embryos

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