Developmental perfluorooctanesulfonic acid exposure impairs exocrine pancreas function in zebrafish (<i>Danio rerio</i>)

Developmental perfluorooctanesulfonic acid (PFOS) exposure in zebrafish reduces digestive gene expression and pancreas length, indicating exocrine insufficiency. This project focuses on the production and function of digestive proteases with PFOS exposure. We test the hypothesis that developmental PFOS exposure impairs exocrine pancreas function in the absence of severe morphological changes. Three larval timepoints were assessed, where the nutrient source varies (yolk feed at 4-d postfertilization [dpf], yolk depleted at 6 dpf, and exogenously fed at 9 dpf) to understand how nutrients were being used throughout exocrine pancreas development. Tg(ptf1a: GFP) zebrafish were exposed to 0 (0.01% DMSO), 1, 2, and 4 μM PFOS from 0 to 4 dpf. At 4 dpf, pancreas length was decreased with 1 μM and yolk sac area was reduced with 2 and 4 μM PFOS. By 6 dpf, pancreata of zebrafish exposed to 1 μM PFOS had recovered, and pancreas size was decreased with 4 μM PFOS. Protease activity was reduced with PFOS exposure, accompanied by decreases in digestive protease gene expression and trypsin protein. At 9 dpf, there was no measurable change in pancreas size or protease activity with 1 and 2 μM PFOS, indicating morphological and functional recovery even though PFOS was detected in the larvae. This study demonstrates that PFOS exposure can affect the function of the exocrine pancreas in the absence of a detectable change in organ size. We also highlight the mishandling of yolk nutrients, leading to undernutrition at later larval stages and show catch-up growth in morphology and function.