Developmental perfluorobutanesulfonic acid (PFBS) exposure alters exocrine pancreas function in zebrafish (Danio rerio).

Abstract

Embryonic exposures to perfluorobutanesulfonic acid (PFBS) in zebrafish have been shown to impair pancreas growth. This study investigated the persistence of the truncated pancreas phenotype, functional impacts on digestive enzyme production, and the hypothesis that redox stress contributes to these outcomes. Transgenic ptf1a:GFP zebrafish were exposed to 0 (0.01% dimethyl sulfoxide (DMSO)), 16, and 32 µM PFBS from 24 to 96 h post-fertilization (hpf) and raised in clean water to 15 days post-fertilization (dpf). Confocal microscopy revealed the pancreata regained normal size, suggesting "catch-up" growth. To evaluate the importance of redox stress in this recovery and acinar cell function, wild-type or mutant zebrafish embryos with a mutation in the DNA-binding domain of the Nrf2a transcription factor were exposed to PFBS from 3 to 96 hpf and raised to 9 dpf in clean water. At 9 dpf, Nrf2a mutants had shorter exocrine pancreases than wild-types with the same treatment, indicating this phenotype likely involves redox stress. Expression of pancreatic proteases and Trypsin were examined to assess functional changes. Although protease gene expression did not differ significantly at 4 or 9 dpf, Trypsin levels decreased with increasing PFBS concentrations in wild-type larvae at 6 and 9 dpf. Lipid analysis showed no change in cholesterol but lower triglycerides in Nrf2a mutants. Assessment of glutathione utilization using monochlorobimane fluorescence indicated more robust antioxidant responses in wild-type fish. This study increases understanding of how Nrf2a modulates the response to PFBS exposure, impacts on exocrine pancreas function, and has implications for understanding "catch-up" growth in response to embryonic toxicant exposures.