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Updated: Jul 15, 2026
In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Identification of gene expression indicators for thyroid axis disruption in a Xenopus laevis metamorphosis screening
Caren C Helbing1, Lan Ji, Carmen M Bailey
1Department of Biochemistry and Microbiology, PO Box 3055, Stn. CSC, University of Victoria, Victoria, British Columbia V8W 3P6, Canada. chelbing@uvic.ca
Abstract:
Thyroid hormones (TH), thyroxine (T(4)) and 3,5,3'-triiodothyronine (T(3)), play crucial roles in regulation of growth, development and metabolism in vertebrates and are targets for endocrine disruptive agents. Perturbations in TH action can contribute to the development of disease states and the US Environmental Protection Agency is developing a high throughput screen using TH-dependent metamorphosis of the Xenopus laevis tadpole as an assay platform. Currently this methodology relies on external morphological endpoints and changes in central thyroid axis parameters. However, exposure-related changes in gene expression in TH-sensitive tissue types that occur over shorter time frames have the potential to augment this screen. Using a combination of cDNA array and real time quantitative polymerase chain reaction (QPCR) analyses, this study identifies molecular markers in tissues peripheral to the central thyroid axis. We examine the hindlimb and tail of tadpoles up to 96 h of continuous exposure to T(3), T(4), methimazole, propylthiouracil, or perchlorate. Several novel biomarker candidates are indicated that include transcripts encoding importin, RNA helicase II/Gu, and defender against death protein, DAD1. In combination with previously-identified biomarker candidates, these transcripts will greatly augment the predictive and diagnostic power of the Xenopus metamorphosis assay for perturbation of TH action.
Insights
This study identifies novel gene expression biomarkers in Xenopus tadpole tissues to improve the detection of thyroid hormone (TH) disruption. These molecular markers enhance the predictive power of the Xenopus metamorphosis assay for endocrine disruptors.
Area of Science:
- Endocrinology
- Developmental Biology
- Toxicology
Background:
- Thyroid hormones (TH), thyroxine (T4) and triiodothyronine (T3), regulate critical physiological processes in vertebrates.
- Endocrine-disrupting agents can interfere with TH action, leading to disease.
- The Xenopus laevis tadpole metamorphosis assay is a high-throughput screening tool for TH disruption.
Purpose of the Study:
- To identify novel molecular markers in peripheral tissues of Xenopus tadpoles exposed to TH or disruptors.
- To augment the existing Xenopus metamorphosis assay with gene expression endpoints.
- To enhance the predictive and diagnostic capabilities for TH action perturbations.
Main Methods:
- Utilized cDNA array and quantitative PCR (QPCR) to analyze gene expression.
- Examined hindlimb and tail tissues from tadpoles exposed to T3, T4, methimazole, propylthiouracil, or perchlorate.
- Assessed gene expression changes within 96 hours of continuous exposure.
Main Results:
- Identified several novel biomarker candidates, including transcripts for importin, RNA helicase II/Gu, and defender against death protein (DAD1).
- These novel markers were found in tissues peripheral to the central thyroid axis.
- The identified transcripts showed potential as early indicators of TH perturbation.
Conclusions:
- Novel gene expression markers can significantly enhance the Xenopus metamorphosis assay.
- These biomarkers provide a more sensitive and rapid assessment of thyroid hormone disruption.
- The findings contribute to improved screening for endocrine-disrupting chemicals affecting TH action.
