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Gene transcription ontogeny of thyroid-axis development in early-life stage fathead minnows (Pimephales promelas)
Cavallin, J., A. Schroeder, T. Saari, J. Swintek, G. Ankley, D. Knapen, K. Nelson, E. Randolph, S. Robinson, L. Vergauwen, AND Dan Villeneuve. Gene transcription ontogeny of thyroid-axis development in early-life stage fathead minnows (Pimephales promelas). SETAC North America, Minneapolis, MN, November 12 - 16, 2017.
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, 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. Abstract: The hypothalamic-pituitary-thyroid (HPT) axis plays a critical role in regulation of metabolism, growth, and development in vertebrates. While the role of the HPT axis and thyroid hormone signaling in mammalian and amphibian development is well established, less is known relative to its role in fish. Baseline understanding of HPT-related mRNA expression may aid in predictions as to when early-life stage fish may be most susceptible to thyroid-disrupting compounds. In the present study, a time-course documenting transcription of key genes associated with the HPT axis over the course of early-life stages of fathead minnow (Pimephales promelas) development was evaluated. Fathead minnow embryos were sampled at eight time points between fertilization and hatch (5 days post-fertilization), and larvae were sampled approximately every other day, from hatch until 28 days post-hatch. Total RNA was extracted from pooled, whole fish, and mRNA transcription of thyroid-related genes was evaluated using quantitative polymerase chain reaction. Gene transcripts examined included: thyrotropin-releasing hormone receptor-2 (trhr2), thyroid stimulating hormone receptor (tshr), sodium-iodide symporter (nis), thyroid peroxidase (tpo), transthyretin (ttr), deiodinases 1 and 2 (dio1 and dio2), and thyroid hormone receptors-alpha and -beta (thr and β). Baseline knowledge of thyroid-related mRNA transcription provided in the present study will aid in the development of adverse outcome pathways detailing impacts of thyroid axis disruption during fish early-life stages and insights into the roles different components of the axis may play during fish development. The contents of this abstract neither constitute nor necessarily reflect US EPA policy.