Reversibility of Thyroid Hormone System-Disrupting Effects on Eye and Thyroid Follicle Development in Zebrafish (Danio rerio) Embryos

Environ Toxicol Chem. 2023 Jun;42(6):1276-1292. doi: 10.1002/etc.5608. Epub 2023 Apr 25.

Abstract

Early vertebrate development is partially regulated by thyroid hormones (THs). Environmental pollutants that interact with the TH system (TH system-disrupting chemicals [THSDCs]) can have massively disrupting effects on this essential phase. Eye development of fish is directly regulated by THs and can, therefore, be used as a thyroid-related endpoint in endocrine disruptor testing. To evaluate the effects of THSDC-induced eye malformations during early development, zebrafish (Danio rerio) embryos were exposed for 5 days postfertilization (dpf) to either propylthiouracil, a TH synthesis inhibitor, or tetrabromobisphenol A, which interacts with TH receptors. Subsequently, one half of the embryos were exposed further to the THSDCs until 8 dpf, while the other half of the embryos were raised in clean water for 3 days to check for reversibility of effects. Continued THSDC exposure altered eye size and pigmentation and induced changes in the cellular structure of the retina. This correlated with morphological alterations of thyroid follicles as revealed by use of a transgenic zebrafish line. Interestingly, effects were partly reversible after a recovery period as short as 3 days. Results are consistent with changes in TH levels measured in different tissues of the embryos, for example, in the eyes. The results show that eye development in zebrafish embryos is very sensitive to THSDC treatment but able to recover quickly from early exposure by effective repair mechanisms. Environ Toxicol Chem 2023;42:1276-1292. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Keywords: Endocrine disruptors; Flame retardant; Histopathology; Propylthiouracil (PTU); Tetrabromobisphenol A (TBBPA); Transgenic line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Endocrine System
  • Thyroid Gland*
  • Thyroid Hormones
  • Water Pollutants, Chemical* / toxicity
  • Zebrafish

Substances

  • Thyroid Hormones
  • Water Pollutants, Chemical