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Gene transcription ontogeny of hypothalamic-pituitary-thyroid-axis development in early-life stage fathead minnow and zebrafish
Vergauwen, L., J. Cavallin, G. Ankley, C. Bars, I. Gabriels, E. Michiels, K. Nelson, J. Periz-Stanacev, E. Randolph, S. Robinson, T. Saari, A. Schroeder, E. Stinckens, J. Swintek, S. Van Cruchten, E. Verbueken, Dan Villeneuve, AND D. Knapen. Gene transcription ontogeny of hypothalamic-pituitary-thyroid-axis development in early-life stage fathead minnow and zebrafish. SETAC Europe, Rome, ITALY, May 13 - 17, 2018.
In order to accurately predict adverse developmental outcomes associated with exposure to thyroid disrupting chemicals on fish and wildlife, it is important to understand the role the thyroid system plays at different stages of development in order to understand the time periods during which they may be most vulnerable. The present study examined the expression of nine genes important to thyroid axis regulation over the course of development in the fathead minnow and zebrafish, two important a model fish species. These data aid the development and interpretation of adverse outcome pathway descriptions that can help translate mechanistically-based high throughput screening data into relevant predictions of hazard for fish. Results of this work should ultimately feed into effort to more effectively employ high throughput screening data in pesticide risk assessments, development of water quality criteria, and risk assessment related to endocrine disruption.
Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in development where that disruption can most readily lead to adverse effects. The present study documents the expression of key genes associated with thyroid hormone signaling and regulation. It provides baseline information that can lead to a more complete understanding of which thyroid disrupting chemicals fish may be susceptible to and at which stages in development. This information enhances our ability to predict effects of endocrine disruptors based on bioactivity measurements that can be made more rapidly and cost effectively than with traditional whole organism toxicity tests. The hypothalamic-pituitary-thyroid (HPT) axis is known to play a crucial role in the development of teleost fish. However, knowledge of endogenous transcription profiles of thyroid-related genes in developing teleosts remains fragmented. We selected two model teleost species, the fathead minnow (Pimephales promelas) and the zebrafish (Danio rerio) to describe the gene transcription ontogeny of the HPT-axis. Control embryos were sampled at several time points between fertilization and hatching, and larvae were sampled approximately every other day until 33 days post-fertilization. Total RNA was extracted from pooled, whole fish, and thyroid-related mRNA expression was evaluated using quantitative polymerase chain reaction. Gene transcripts examined included: thyrotropin-releasing hormone receptor (trhr), thyroid-stimulating hormone receptor (tshr), sodium-iodide symporter (nis), thyroid peroxidase (tpo), thyroglobulin (tg), transthyretin (ttr), deiodinases 1, 2, 3a, and 3b (dio1, dio2, dio3a and 3b), and thyroid hormone receptors alpha and beta (thr and â). A loess regression method was successful in identifying maxima and minima of transcriptional expression during early development of both species. Overall, we observed great similarities between both species, including maternal transfer of almost all transcripts (confirmed in unfertilized eggs), increasing expression of most transcripts during hatching and embryo-larval transition, and indications of a fully functional HPT-axis in larvae. By making these data available to the community, we aim to aid in the development of hypotheses on the role of certain genes and pathways during development. Furthermore, it can function as a background reference dataset for designing and interpreting targeted transcriptional expression studies both for fundamental research and for applications, such as ecotoxicology.