Potential Endpoints to Identify Thyroid Hormone System Disruption in Zebrafish Embryos

Lisa Gölz, Henrik Holbech, Thomas Braunbeck, Lucia Vergauwen, Dries Knapen, Lisa Baumann

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskning

Abstract

Identifying thyroid hormone system disruptors (THSD) is warranted because of the crucial role that thyroid hormones (THs) play in the normal development of vertebrates. Thus, selection of a sensitive animal model and identification of suitable endpoints for detecting THSDs are key for guiding regulatory decisions. OECD fish test guidelines so far lack TH system sensitive endpoints. However, the TH system regulates a wide range of measurable molecular and morphological endpoints in fish, including swim bladder inflation, thyroid- and eye-related gene expression, and the development of thyroid follicles and eyes. This study aimed to investigate whether these endpoints are suitable for detecting THSD in the zebrafish (Danio rerio) embryo by using the existing OECD test guideline 236 (FET, fish embryo toxicity test). We performed experiments with multiple THSDs with different modes-of-action, such as propylthiouracil (PTU), potassium perchlorate (PCL), iopanoic acid (IOP) and the natural thyroid hormone triiodothyronine (T3). The basic protocol of OECD TG 236 was followed, and different TH system sensitive endpoints such as gene expression, detection of cellular changes in the eyes (e.g., cell size, cell layer structure and organization, number of photoreceptors, pigmentation etc.), as well as morphological changes (e.g., alterations of thyroid follicular morphology in transgenic fish) were added. For thyroidal analysis, transgenic zebrafish embryos expressing the reporter gene tg:mCherry were used. Results demonstrate that zebrafish embryos react sensitively to THSD. Changes in the expression of the eye- and thyroid-related genes in the zebrafish embryos were observed and different modes of THSD resulted in various alterations of thyroid follicle morphology and fluorescence intensity in the transgenic line. Furthermore, strong alterations of eye morphology and cellular structure, combined with changes in photoreceptor patterning, could be recorded by (immuno- )histopathology. Results confirm growing evidence that zebrafish embryos are sensitive to THSD treatment and represent a promising tool for assessing TH system- related effects in fish. The FET protocol according to OECD TG 236 proved to be a suitable basis for implementing TH system sensitive endpoints in fish, as it covers important stages of early development, many of which are regulated by THs.
OriginalsprogEngelsk
Publikationsdato3. maj 2023
StatusUdgivet - 3. maj 2023
BegivenhedSETAC Europe 33rd Annual meeting: Data-driven environmental decision-making - the Convention Centre Dublin, Dublin, Irland
Varighed: 30. apr. 20234. maj 2023
https://europe2023.setac.org/

Konference

KonferenceSETAC Europe 33rd Annual meeting
Lokation the Convention Centre Dublin
Land/OmrådeIrland
ByDublin
Periode30/04/202304/05/2023
Internetadresse

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