Parental exposure to tebuconazole causes thyroid endocrine disruption in zebrafish and developmental toxicity in offspring

Abstract Azole fungicides are one class of the most extensively applied current-use pesticides. Tebuconazole is a common azole fungicide that has been frequently detected in aquatic ecosystems, thus raising concerns about its ecological safety. However, adverse effects of tebuconazole remain largely unknown, especially with regard to endocrine function in aquatic organisms. In the present study, sexually immature zebrafish were exposed to different concentrations of tebuconazole (0.05, 0.20 and 0.50 mg/L) for 60 days in order to test for transgenerational toxicity on the thyroid endocrine system. Thyroid hormone homeostasis, neuronal, and cardiovascular development were investigated in the F1 generation, which were reared in tebuconazole-free water. In the F0 generation, exposure to 0.20 and 0.50 mg/L tebuconazole reduced both thyroxine (T 4 ) and 3,5,3’-triiodothyronine (T 3 ) levels in females, while the T 3 levels were unchanged in males. Decreased heart rate was found in F1 larvae, as well as diminished T 4 levels in F1 eggs/larvae. We also observed significantly increased expression of ugt1ab mRNA in two generations of zebrafish. Moreover, expression of mRNA associated with neuronal development (e.g. α1-tubulin , mbp , ga p43) and cardiovascular development (e.g. cacna1ab , tnncal ) were significantly downregulated in F1 larvae at 5 and 10 dpf. In addition, tebuconazole was detected in F1 eggs following parental exposure, indicating maternal transfer. This study demonstrated that tebuconazole can be transferred to offspring from exposed parents, causing thyroid endocrine disruption and developmental toxicity.