Zebrafish: a key model for unraveling endocrine-disrupting effects on thyroid development and function

The zebrafish (<i>Danio rerio</i>) has emerged as a crucial vertebrate model for studying thyroid physiology and toxicology, owing to its high genomic homology with mammals, external embryogenesis, transparent development, and the availability of advanced genetic manipulation techniques. Moreover, this experimental system is widely used for toxicity testing of environmental chemical compounds that affect thyroid function, yielding well-characterized phenotypic and molecular responses. It is well known that thyroid hormones regulate embryonic development in vertebrates, particularly the development of the central nervous system. Moreover, thyroid hormones control energy metabolism, growth, cellular differentiation, and overall homeostasis, physiological processes conserved in both zebrafish and mammal models. Therefore, this mini-review provides a comprehensive analysis of the current literature regarding the use of zebrafish to investigate the effects of endocrine-disrupting chemicals on the hypothalamic-pituitary-thyroid axis and thyroid function, as well as the associated physiological and behavioral responses. This review also discusses the limitations of the zebrafish model, including the challenges of establishing exposure models that are realistic and comparable to those experienced by humans and other animals in the environment. Finally, it discusses the intra- and intergroup variability, technical challenges in molecular analyses at early developmental stages, anatomical differences relative to humans, and difficulties in experimental handling and reproducibility. Nevertheless, zebrafish is an undeniable, versatile, and powerful model for advancing research in thyroid endocrinology and toxicology, especially during critical developmental windows, which are more complex to assess in mammals.