Related Experiment Video
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, Carmen M Bailey, Lan Ji
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 their actions 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 amphibian metamorphosis 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. This study aims to characterize and identify molecular markers in the tadpole brain. Using a combination of cDNA array analysis and real time quantitative polymerase chain reaction (QPCR), we examine the brain of tadpoles following 96 h of continuous exposure to T(3), T(4), methimazole, propylthiouracil, or perchlorate. This tissue was more sensitive to T(4) rather than T(3), even when differences in biological activity were taken into account. This implies that a simple conversion of T(4) to T(3) cannot fully account for T(4) effects on the brain and suggests distinctive mechanisms of action for the two THs. While the brain shows gene expression alterations for methimazole and propylthiouracil, the environmental contaminant, perchlorate, had the greatest effect on the levels of mRNAs encoding proteins important in neural development and function. Our data identify gene expression profiles that can serve as exposure indicators of these chemicals.
Insights
Thyroid hormones (T4 and T3) are vital for vertebrate development. This study found perchlorate significantly altered gene expression in tadpole brains, identifying potential biomarkers for endocrine disruptors.
Area of Science:
- Endocrinology and Toxicology
- Molecular Biology
- Developmental Biology
Background:
- Thyroid hormones (TH), including thyroxine (T4) and triiodothyronine (T3), regulate critical physiological processes in vertebrates.
- Endocrine-disrupting agents can interfere with TH action, potentially leading to disease.
- Current high-throughput screening methods for TH disruption rely on external endpoints, but gene expression changes offer a more sensitive, earlier indicator.
Purpose of the Study:
- To identify molecular markers in tadpole brains indicative of thyroid hormone disruption.
- To evaluate the sensitivity of brain gene expression to different thyroid hormones and chemical exposures.
- To assess the potential of gene expression profiles as early indicators for endocrine disruptors.
Main Methods:
- Tadpole brains were exposed to T3, T4, methimazole, propylthiouracil, or perchlorate for 96 hours.
- Gene expression analysis was performed using cDNA array analysis and quantitative polymerase chain reaction (QPCR).
- Changes in mRNA levels encoding proteins involved in neural development and function were quantified.
Main Results:
- The tadpole brain tissue demonstrated higher sensitivity to T4 than T3, suggesting distinct mechanisms of action beyond simple conversion.
- Methimazole and propylthiouracil caused alterations in brain gene expression.
- The environmental contaminant perchlorate exhibited the most significant impact on mRNA levels crucial for neural development and function.
Conclusions:
- Gene expression profiling in tadpole brains can serve as a sensitive assay for detecting thyroid hormone disruptors.
- Perchlorate significantly affects neural gene expression, highlighting its potential as an endocrine disruptor.
- Distinct mechanisms for T4 and T3 action in the brain are suggested by differential sensitivity.
More Related Videos
11:13Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo
Published on: February 2, 2016
09:07Fluorescent Calcium Imaging and Subsequent In Situ Hybridization for Neuronal Precursor Characterization in Xenopus laevis
Published on: February 18, 2020