An assay to determine the sensitive window of embryos to chemical exposure using <i>Xenopus tropicalis</i>

Hu, Lingling; Wu, Lijiao; Xue, Yingang; Zhu, Jingmin; Shi, Huahong

doi:10.1002/jat.3200

Cited by 5 publications

(1 citation statement)

References 28 publications

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“…Long-term exposure experiments make it difficult to link the exact function of RXRs and the teratogenic characteristics of chemicals. For example, the RXR antagonists UVI3003 and HX531 induced divergent malformations in X. tropicalis embryos following 12 hrs of exposure (Hu et al, 2015b). Therefore, identifying stage-specific gene expression changes in response to RXR antagonists should be useful in shedding light on teratogenic mechanisms in X. tropicalis .…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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Xenopus as an Experimental Organism

Tadjuidje

2022

Encyclopedia of Life Sciences

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The South African clawed frog, Xenopus laevis , is a popular model system to study development. It is easy to maintain a breeding frog colony, females can be spawned all year round and hundreds of synchronously growing embryos can be generated from a single fertilisation. Embryos are easily amenable to microsurgery at any stage of development and adults survive surgeries performed under limited aseptic conditions. The ease of injecting oligonucleotides or messenger ribonucleic acid (mRNA) into Xenopus leavis embryos has contributed to the discovery of genes with key functions in development. Another singularity of Xenopus leavis is the ease to manipulate its oocytes before fertilisation; this has been a powerful tool to identify the function of maternally deposited mRNAs in development. Over the past two decades, transgenic strategies have been developed using the related species Xenopus tropicalis and this is broadening the contribution of Xenopus to the understanding of early development. Key Concepts Xenopus laevis is easy to raise and feed in large colonies in the lab, and commercial vendors can now supply frogs and embryos at all developmental stages for research. The female Xenopus can be induced to spawn repeatedly at any season, making it possible to obtain embryos all year round. Xenopus leavis' eggs are large, they measure around 1.3 mm in diameter and are usually laid in large numbers that are fertilised in vitro . The Xenopus embryos develop outside the female, its early development is very fast, making it possible to study a full developmental program in about 3 days, with the possibility to manipulate the embryos at any stage of development. Xenopus leavis oocytes can easily be obtained and manipulated before fertilisation, making it possible to study the function of maternally deposited mRNAs. The mechanisms of tissue and body axis formation have been elucidated from research carried out in Xenopus leavis embryos, and a Xenopus toxicological test called FETAX has been recommended by scientists from the American Food and Drug Administration, for the teratogenic screening of new drugs candidates. Gene editing techniques have been developed for Xenopus, making it an excellent model to mimic human mutations and study human diseases like cancers and congenital diseases. The sequencing of the diploid genome, ease of obtaining and injecting large numbers of eggs and the relatively short lifespan makes Xenopus tropicalis a very powerful model for gene editing and transgenic studies of organogenesis. Eggs of Xenopus leavis provide a model of choice for studying the regulation of the cell cycle. A database called Xenbase is now available to the Xenopus research community; it contains usefully and regularly updated information on Xenopus research and resources.

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Microscopic photoplethysmography‐based evaluation of cardiotoxicity in whitefish larvae induced by acute exposure to cadmium and phenol

Machikhin,

Guryleva,

Chakraborty

et al. 2024

Journal of Biophotonics

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Toxic environmental pollutants pose a health risk for both humans and animals. Accumulation of industrial contaminants in freshwater fish may become a significant threat to biodiversity. Comprehensive monitoring of the impact of environmental stressors on fish functional systems is important and use of non‐invasive tools that can detect the presence of these toxicants in vivo is desirable. The blood circulatory system, by virtue of its sensitivity to the external stimuli, could be an informative indicator of chemical exposure. In this study, microscopic photoplethysmography‐based approach was used to investigate the cardiac activity in broad whitefish larvae (Coregonus nasus) under acute exposure to cadmium and phenol. We identified contamination‐induced abnormalities in the rhythms of the ventricle and atrium. Our results allow introducing additional endpoints to evaluate the cardiac dysfunction in fish larvae and contribute to the non‐invasive evaluation of the toxic effects of industrial pollutants on bioaccumulation and aquatic life.

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An assay to determine the sensitive window of embryos to chemical exposure using Xenopus tropicalis

Cited by 5 publications

References 28 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

Xenopus as an Experimental Organism

Microscopic photoplethysmography‐based evaluation of cardiotoxicity in whitefish larvae induced by acute exposure to cadmium and phenol

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