Dysregulation of circadian rhythm in zebrafish (Danio rerio) by thifluzamide: Involvement of positive and negative regulators

     Thifluzamide as a fungicide is toxic to brain of zebrafish embryos. Brain can regulate biological rhythms.To clarify whether thifluzamide would influence circadian rhythms, zebrafish embryos were treated with thifluzamide (0, 0.19, 1.90 and 2.85 mg/L) for 4 days. Exposure to thifluzamide induced pronounced changes in embryo brain and melatonin levels. The mRNA levels of genes related to circadian rhythms were apparently altered. Among these, the transcripts of cry1ba and clock1 were extremely correlated with exposure concentrations. Importantly, the content of cry1 showed no apparent changes, but the clock level was dramatically increased. Moreover, consistent with the inhibition of development and behavior, the levels of GH and DA were significantly inhibited. In addition, the expression levels of genes related to development, behavior and reproduction were significantly changed by thifluzamide. Therefore, we speculated that circadian disruption due to thifluzamide exposure were primarily attributed to increases in expression of clock1a and contents of clock, which might be at least in part responsible for abnormal development and behavior of zebrafish. In addition, our research will provide important insights into the grouped assessment of SDHI pesticides in future.