Dioxin Exposure Alters Molecular and Morphological Responses to Thyroid Hormone in Xenopus laevis Cultured Cells and Prometamorphic Tadpoles

Toxicological Sciences : an Official Journal of the Society of Toxicology
Justin D TaftWade H Powell

Abstract

Amphibian metamorphosis is driven by thyroid hormone (TH). We used prometamorphic tadpoles and a cell line of the African clawed frog (Xenopus laevis) to examine immediate effects of dioxin exposure on TH. Gene expression patterns suggest cross-talk between the thyroid hormone receptor (TR) and aryl hydrocarbon receptor (AHR) signaling pathways. In XLK-WG cells, expression of Cytochrome P450 1A6 (cyp1A6), an AHR target, was induced 1000-fold by 100 nM TCDD (2, 3, 7, 8 tetrachlorodibenzo-p-dioxin). Krüppel-Like Factor 9 (klf9), the first gene induced in a cascade of TH responses tied to metamorphosis, was upregulated over 5-fold by 50 nM triiodothyronine (T3) and 2-fold by dioxin. Co-exposure to T3 and TCDD boosted both responses, further inducing cyp1A6 by 75% and klf9 about 60%. Additional canonical targets of each receptor, including trβa and trβb (TR) and udpgt1a (AHR) responded similarly. Induction of TH targets by TCDD in XLK-WG cells predicts that exposure could speed metamorphosis. We tested this hypothesis in two remodeling events: tail resorption and hind limb growth. Resorption of ex vivo cultured tails was accelerated by 10 nM T3, while a modest increase in resorption by 100 nM TCDD lacked statistical significance. H...Continue Reading

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Citations

Feb 26, 2019·Acta Microbiologica Et Immunologica Hungarica·György Csaba
Oct 16, 2019·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Marissa FabreziJulio César Cruz
Apr 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·Christophe RegnaultStéphane Reynaud
Mar 10, 2020·Molecular and Cellular Endocrinology·Stephan CouderqJean-Baptiste Fini

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