Developmental Toxicity of Sodium Iodide Using the Zebrafish Model

Iodine is considered an essential nutrient as lack can cause severe metabolic and neurological issues in adults, with the added consequence of permanent developmental damage in children and infants. However, excessive iodine intake can result in similar symptoms, with a wide variance in adverse health outcomes. The safe range of iodine intake may be relatively low, with some studies suggesting the possibility of a high frequency of subclinical cases of iodine poisoning going unnoticed or misdiagnosed.

In this study, the zebrafish model was tested as an integrative whole animal model to demonstrate behavioral, morphological, and genetic responses to overt and subclinical iodine poisoning in developing humans. Zebrafish embryos were treated with sodium iodide (NaI) immediately after fertilization. Survivability was monitored every 24 hours until 120 hours post fertilization (hpf). Concentrations with no statistical significance on survival, plus the smallest dose of significant lethality were then examined using behavioral analysis at 120 hpf to compare both overt and subclinical outcomes. Morphology measurements of body length, head length, head width, brain length, swim bladder volume, jaw length, and ventral dissension were also recorded at 120 hpf. Gene expression of slc5a5, tpo, and tshba at 72 hpf was also measured using quantitative PCR (qPCR).

A significant decrease in survival rates were observed at 24 hpf for 25, 37.5, and 50 mM NaI treatments (p<0.0001). Morphological measurements taken at 120 hpf showed a significant increase in body length, head length, head width, jaw length, and swim bladder volume in the 10 mM NaI treatment group (p<0.0001) and a significant decrease in body length, head length, jaw length, and swim bladder volume in the 25 mM treatment group (p<0.0001). A ventral distension also developed near the location of the thyroid gland exclusively in the 25 mM group.

Behavioral analysis showed significant increases in movement for both the 10 mM and 25 mM treatment groups during dark phases (p<0.0001). The 25 mM treatment group had an increase in movement during dark phases for standard well environments (p<0.0001), but this did not hold true for larger well environments, instead trending towards a non-significant decrease (p>0.05). The 10 mM group had a significant decrease during the first light phase in standard wells (p=0.002), with a significant increase in the second light phase for large wells (p=0.005). There were no significant changes in the expression of selected genes associated with the thyroid pathway (slc5a5, tpo, or tshba) across all treatment groups (p>0.05).

Overall, the results suggest zebrafish larvae exhibit both overt and subclinical symptoms of excess iodine intake. Future studies are needed to determine internalization, biodistribution, clearance, and further characterization of adverse outcomes along the thyroid pathway for additional exploration into subclinical thyrotoxicosis due to excess iodine intake. Researchers should express caution with time points, as the Wolff-Chaikoff effect may influence exposure windows in zebrafish.