|ZFIN ID: ZDB-PUB-150924-9|
Deviant development of pancreatic beta cells from embryonic exposure to PCB-126 in zebrafish
Timme-Laragy, A.R., Sant, K.E., Rousseau, M.E., diIorio, P.J.
|Source:||Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 178: 25-32 (Journal)|
|Registered Authors:||diIorio, Philip|
|Keywords:||Ahr, Nrf2, embryo, endocrine, gene expression, insulin, islet, time-lapse|
|PubMed:||26393762 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.|
Timme-Laragy, A.R., Sant, K.E., Rousseau, M.E., diIorio, P.J. (2015) Deviant development of pancreatic beta cells from embryonic exposure to PCB-126 in zebrafish. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. 178:25-32.
ABSTRACTExposures to co-planar PCBs and dioxins have been associated with diabetes in epidemiologic studies. Individuals may be predisposed to diseases such as diabetes as a result of exposure to environmental contaminants during early life, resulting in dysmorphic pancreatic islets or metabolically fragile β-cells. We tested the hypothesis that embryonic exposure to a model Ahr-ligand, PCB-126 would cause structural and/or functional alterations to the developing primary pancreatic islet in the zebrafish (Danio rerio). To assess β-cell development, transgenic zebrafish embryos (Tg(ins:GFP) and Tg(ins:mcherry) were exposed to nominal concentrations of 2 or 5 nM PCB-126 or DMSO from 24-48 hours post fertilization (hpf), and imaged via time-lapse microscopy from 80-102 hpf. We identified defects including hypomorphic islets, altered islet migration, islet fragmentation, and formation of ectopic β-cells. As we recently showed the transcription factor Nrf2a is protective in PCB-126 embryotoxicity, we then assessed the transcriptional function of the islets in wildtype and nrf2a(fh318/fh318) mutant embryos. We measured gene expression of preproinsulin a, somatostatin2, pdx1, ghrelin, and glucagon. Expression of preproinsulin a increased with PCB treatment in wildtype embryos, while expression of all measured pancreas genes was altered by the nrf2a mutant genotype, suggesting mis-regulation of the glucose homeostasis axis in those embryos, independent of PCB treatment. This study shows that embryonic exposure to PCB-126 can result in deviant development of the pancreatic islet and suggests that Nrf2a plays a role in regulating glucose homeostasis during development.