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Brain samples in a metamorphosis assay for thyroid axis disruption

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Xenopus laevis Aquarana catesbeiana

PROVIDER: GSE7189 | GEO | 2007/05/12

SECONDARY ACCESSION(S): PRJNA98227

REPOSITORIES: GEO

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

Project description: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: dose response

2007-05-12 | GSE7057 | GEO

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

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Expression data for hindlimb and tail samples in a metamorphosis assay for thyroid axis disruption - inhibitors

Project description:Thyroid hormones (TH), thyroxine (T4) and 3, 5, 3’-triiodothyronine (T3), 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 U.S. 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 hours of continuous exposure to T3, T4, 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. Keywords: time course

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Amphibian Metamorphosis Assay: Investigation of the potential effects of five chemicals on the hypothalamic-pituitary thyroid axis of Xenopus laevis.

Project description:2-Ethylhexyl 4-hydroxybenzoate (2-EHHB), 4-tert-octylphenol (4-OP), 4-nonylphenol-branched (4-NP), benzyl butyl phthalate (BBP) and dibutyl phthalate (DBP) were evaluated using a 21-day Amphibian Metamorphosis Assay (AMA). Xenopus laevis larvae were exposed nominally to each chemical at 3.6, 10.9, 33.0, and 100 μg/L, except 4-NP concentrations were 1.8, 5.5, 16.5 and 50 μg/L. Endpoints included mortality, developmental stage, hind limb length (HLL), snout-vent length (SVL), body weight (BW), and thyroid histopathology. BBP and 4-OP accelerated development compared to controls at the mean measured concentration of 3.5 and 39.8 μg/L, respectively. An increase in developmental stage frequency distribution was observed for 4-OP at 39.8 and 103 µg/L, BBP at all concentrations and DBP at 143 µg/L. Normalized HLL was increased on study day (SD) 21 for all tested substances except 4-NP. Histopathology revealed accelerated development and mild thyroid follicular cell hypertrophy at all BBP concentrations, but moderate severity at 105 μg/L. Increased BW occurred for all chemicals except 4-OP. Increased SVL was observed for 4-NP, BBP and DBP on SD 21. There was insufficient evidence that 4-NP and 2-EHHB affected the hypothalamic-pituitary thyroid axis, however, BBP, DBP and 4-OP showed potential effects on amphibian metamorphosis and thyroid activity, albeit through different lines of evidence.

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