Tompach Madeline C, Gridley Charlotte K, Marin Marjorie, Murphy Patrick F, Lee Junghak, Clark John M, Timme-Laragy Alicia R
Molecular and Cellular Biology Graduate Program, University of Massachusetts Amherst, Amherst, MA 01003, United States.
Biotechnology Training Program, University of Massachusetts Amherst, Amherst, MA 01003, United States.
Toxicol Sci. 2025 Jul 1;206(1):46-57. doi: 10.1093/toxsci/kfaf041.
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.
斑马鱼发育过程中暴露于全氟辛烷磺酸(PFOS)会降低消化基因表达并缩短胰腺长度,表明存在外分泌功能不全。本项目聚焦于PFOS暴露情况下消化蛋白酶的产生和功能。我们检验了这样一个假设:发育过程中暴露于PFOS会在无严重形态变化的情况下损害外分泌胰腺功能。评估了三个幼体时间点,此时营养来源不同(受精后4天[4 dpf]为卵黄喂养,6 dpf时卵黄耗尽,9 dpf时开始外源喂养),以了解在外分泌胰腺发育过程中营养物质是如何被利用的。将Tg(ptf1a: GFP)斑马鱼从0至4 dpf暴露于0(0.01%二甲基亚砜)、1、2和4 μM的PFOS中。在4 dpf时,1 μM的PFOS使胰腺长度减小,2和4 μM的PFOS使卵黄囊面积减小。到6 dpf时,暴露于1 μM PFOS的斑马鱼胰腺已恢复,而4 μM PFOS使胰腺大小减小。PFOS暴露使蛋白酶活性降低,同时消化蛋白酶基因表达和胰蛋白酶蛋白减少。在9 dpf时,1和2 μM PFOS对胰腺大小或蛋白酶活性没有可测量的变化,这表明即使在幼体中检测到PFOS,其形态和功能也已恢复。本研究表明,PFOS暴露可在器官大小无明显变化的情况下影响外分泌胰腺的功能。我们还强调了卵黄营养物质的不当处理,导致幼体后期营养不足,并显示出形态和功能上的追赶生长。