PW09 Pesticide I
8:00 AM - Wednesday
(PW163) Fipronil exposure causes notochord degeneration in developing zebrafish embryos.
Stehr, C1, Linbo, T1, Incardona, J1, Scholz, N1, 1 Northwest Fisheries Science Center, NOAA Fisheries, Seattle, WA, USA
ABSTRACT- Fipronil is a phenyl pyrazole insecticide that selectively inhibits insect gamma-aminobutyric acid (GABA) receptors. Although fipronil is widely used in the United States, there are few studies that have assessed its effects on fish and other aquatic organisms. Here we explore the developmental toxicity of fipronil using the zebrafish (Danio rerio) model system. Zebrafish, which complete embryogenesis in 3 days, were exposed to fipronil (0.003-5 mg/L, 24-hr static renewal) shortly after fertilization to 5 days. The morphology of embryos was normal up to 24 hours post-fertilization (hpf) at all exposure concentrations. However, by 48 hpf, anatomical and behavioral abnormalities were apparent in embryos exposed to fipronil at concentrations of 100 
g/L or higher. Affected embryos showed patchy to complete degeneration of the notochord at concentrations of 100 g/L and 5 mg/L, respectively. Reduced locomotor activity was also evident at exposure concentrations starting at 333 g/L. While locomotor deficits are most likely due to the action of fipronil on GABA receptors, there is no known role of GABA receptors in notochord development or function. Thus notochord degeneration may reflect a non-target effect of fipronil. Mechanisms underlying fipronil-induced notochord degeneration were investigated by monitoring the expression of notochord-specific proteins/genes (laminin, collagen 2A1, brachyury, hedgehog family members) and markers of notochord function (e.g. patterning of engrailed+ muscle pioneer cells). Putative contributions of GABA receptor function to notochord development were evaluated by comparing the effects of fipronil to other (non-insecticide) pharmacological GABA antagonists.
Key words: zebrafish, fipronil, development, notochord