Transcriptomics,Genomics

Dataset Information

28

Expression data for brain samples in a metamorphosis assay for thyroid axis disruption - inhibitors


ABSTRACT: Thyroid hormones (TH), thyroxine (T4) and 3, 5, 3’-triiodothyronine (T3), play crucial roles in regulation of growth, development and metabolism in vertebrates and their action are targets for endocrine disruptive agents. Perturbations in TH action can contribute to the development of disease states and the U.S. 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 hours of continuous exposure to T3, T4, methimazole, propylthiouracil, or perchlorate. This tissue was more sensitive to T4 rather than T3, even when differences in biological activity were taken into account. This implies that a simple conversion of T4 to T3 cannot fully account for T4 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. Keywords: time course Overall design: NF stage 54 tadpoles were continuously exposed to a single concentration of PTU (20 mg/L), MMI (100 mg/L) or PER (4 mg/L). We have previously shown that exposure to these concentrations resulted in an increase in thyroid gland size at day 8 and significantly delayed metamorphosis at 14 days (Degitz et al., 2005; Tietge et al., 2005). The exposure regimen details are recorded elsewhere (Zhang et al., 2006). Briefly, tadpoles were randomly placed into 24 tanks (20 tadpoles/tank) and exposed (six tanks/chemical) to a single concentration of each chemical. At 24 h, 48 h and 96 h 5 tadpoles from two of the 6 tanks (10 tadpoles per each individual treatment) were randomly selected, euthanized in MS-222, and preserved in RNAlater (Ambion Inc., Austin, Texas, USA) for analysis of gene expression.

INSTRUMENT(S): UVicHelbing XenRanaMAGEX 434 ver1

SUBMITTER: Caren C Helbing  

PROVIDER: GSE6964 | GEO | 2007-05-12

SECONDARY ACCESSION(S): PRJNA104133

REPOSITORIES: GEO

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Publications

Identification of gene expression indicators for thyroid axis disruption in a Xenopus laevis metamorphosis screening assay. Part 1. Effects on the brain.

Helbing Caren C CC   Bailey Carmen M CM   Ji Lan L   Gunderson Mark P MP   Zhang Fang F   Veldhoen Nik N   Skirrow Rachel C RC   Mu Ruixia R   Lesperance Mary M   Holcombe Gary W GW   Kosian Patricia A PA   Tietge Joseph J   Korte Joseph J JJ   Degitz Sigmund J SJ  

Aquatic toxicology (Amsterdam, Netherlands) 20070223 4


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 mor  ...[more]

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