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Effect of thyroperoxidase and deiodinase inhibition on anterior swim bladder inflation in the zebrafish
Citation:
Stinckens, E., L. Vergauwen, B. Blackwell, G. Ankley, Dan Villeneuve, AND D. Knapen. Effect of thyroperoxidase and deiodinase inhibition on anterior swim bladder inflation in the zebrafish. ENVIRONMENTAL SCIENCE & TECHNOLOGY. American Chemical Society, Washington, DC, 54(10):6213-6223, (2020). https://doi.org/10.1021/acs.est.9b07204
Impact/Purpose:
To address concerns about chemicals in the environment that may interact with the endocrine system and cause adverse effects in vertebrates, EPA has developed screening assays to identify chemicals with endocrine activity. EPA has recently developed high throughput assays that can detect chemicals that inhibit thyroid peroxidase and deiodinases, enzymes important to the synthesis and activation of thyroid hormone. To complement these assays, adverse outcome pathways that provide a scientifically supported description of how these biological activities can lead to adverse effects in humans and wildlife. The present study contributes additional evidence supporting the linkage between inhibition of thyroid peroxidase or deiodinase enzyme activities and impaired inflation of the swim bladder in fish, which can lead to subsequent effects on swimming performance and young of year survival. These studies help to establish the relevance of screening assays for identifying chemicals that may be expected to cause adverse effects through endocrine disrupting modes of action, thereby supporting the needs of the Office of Chemical Safety and Pollution Prevention and Office of Water to implement an endocrine disruptor screening program (EDSP).
Description:
It was previously hypothesized that chemicals that inhibit key enzymes involved in thyroid hormone synthesis or activation (e.g., thyroid peroxidase or deiodinases) could impair swim bladder inflation during fish development, with subsequent effects on swimming performance. The present study provides evidence in support of that hypothesis using three endocrine active chemicals known to impact these enzymes. Together, these results strengthen the ability to screen chemicals for thyroid disrupting biological activities and link those activities to hazards of ecological significance. Such data help to support the use of alternatives to traditional animal testing in endocrine disruptor screening. A set of adverse outcome pathways (AOPs) linking inhibition of thyroperoxidase and deiodinase to impaired swim bladder inflation in fish has recently been developed. These AOPs help to establish links between these thyroid hormone (TH) disrupting molecular events and adverse outcomes relevant to aquatic ecological risk assessment. Until now, very few data on the effects of TH disruption on inflation of the anterior chamber (AC) of the swim bladder were available. The present study used zebrafish exposure experiments with three model compounds with distinct thyroperoxidase and deiodinase inhibition potencies (methimazole, iopanoic acid and propylthiouracil) to evaluate this linkage. Exposure to all three chemicals decreased whole body triiodotyrosine (T3) concentrations, either through inhibition of thyroxine (T4) synthesis or through inhibition of Dio mediated conversion of T4 to T3. A quantitative relationship between reduced T3 and reduced AC inflation was established, a critical key event relationship linking impaired swim bladder inflation to TH disruption. Reduced inflation of the AC was directly linked to reductions in swimming distance compared to controls as well as to chemical-exposed fish whose ACs inflated. Together the data provide compelling support for AOPs linking TH disruption to impaired AC inflation in fish.
URLs/Downloads:
DOI: Effect of thyroperoxidase and deiodinase inhibition on anterior swim bladder inflation in the zebrafish