Parental exposure to propiconazole at environmentally relevant concentrations induces thyroid and metabolism disruption in zebrafish (Danio rerio) offspring: An in vivo, in silico and in vitro study

Propiconazole is used against fungal growth in agriculture and is released into the environment, but is a potential health threat to aquatic organisms. Propiconazole induces a generational effect on zebrafish, although the toxic mechanisms involved have not been described. The aim of this study was to investigate the potential mechanisms of abnormal offspring development after propiconazole exposure in zebrafish parents. Zebrafish were exposed to propiconazole at environmentally realistic concentrations (0.1, 5, and 250 mu g/L) for 100 days and their offspring were grown in control solution for further study. Heart rate, hatching rate, and body length of hatched offspring were reduced. An increase in triiodothyronine (T-3) content and the T-3/T-4 (tetraiodothyronine) ratio was observed, indicating disruption of thyroid hormones. Increased protein level of transthyretin (TTR) in vivo was consistent with the in silico molecular docking results and T-4 competitive binding in vitro assay, suggests higher binding affinity between propiconazole and TTR, more than with T-4. Increased expression of genes related to the hypothalamus-pituitary-thyroid (HPT) axis and altered metabolite levels may have affected offspring development. These findings emphasizes that propiconazole, even on indirect exposure, represents health and environmental risk that should not be ignored.