Identification of gene expression indicators for thyroid axis disruption in a Xenopus laevis metamorphosis screening assay: Part 2. Effects on the tail and hindlimb

• Published in: Aquatic toxicology 2007-05, Vol.82 (4), p.215-226
• Main Authors: Helbing, C.C, Ji, L, Bailey, C.M, Veldhoen, N, Zhang, F, Holcombe, G.W, Kosian, P.A, Tietge, J, Korte, J.J, Degitz, S.J
• Format: Article
• Language: English
• Subjects: Amphibia. Reptilia; Animal, plant and microbial ecology; Animals; Antithyroid Agents - pharmacology; Applied ecology; bioassays; Biological and medical sciences; Biological Assay; biomarkers; brain; complementary DNA; defender against death protein; Ecotoxicology, biological effects of pollution; endocrine-disrupting chemicals; Environmental Monitoring - methods; Environmental Protection Agency; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression Profiling - veterinary; Gene Expression Regulation, Developmental - drug effects; General aspects; Hindlimb - drug effects; Karyopherins - analysis; Karyopherins - biosynthesis; Keratins - analysis; Keratins - biosynthesis; laboratory animals; lakes; limbs (animal); mechanism of action; messenger RNA; Metallothionein - analysis; Metallothionein - biosynthesis; metamorphosis; Metamorphosis, Biological - drug effects; methimazole; microarray technology; Oligonucleotide Array Sequence Analysis - veterinary; perchlorates; polymerase chain reaction; prediction; propylthiouracil; proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA helicase II; RNA helicases; screening; tadpoles; tail; Tail - drug effects; thyroid gland; Thyroid Gland - drug effects; thyroid hormones; Thyroid Hormones - agonists; Thyroid Hormones - physiology; thyroxine; Thyroxine - pharmacology; transcription (genetics); triiodothyronine; Triiodothyronine - pharmacology; Vertebrates: general zoology, morphology, phylogeny, systematics, cytogenetics, geographical distribution; water pollution; Xenopus laevis; Xenopus laevis - physiology
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2007.02.014

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 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 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.