PUBLICATION
Deviant development of pancreatic beta cells from embryonic exposure to PCB-126 in zebrafish
- Authors
- Timme-Laragy, A.R., Sant, K.E., Rousseau, M.E., diIorio, P.J.
- ID
- ZDB-PUB-150924-9
- Date
- 2015
- 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
- MeSH Terms
-
- Animals
- Animals, Genetically Modified/embryology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/embryology
- GA-Binding Protein Transcription Factor/genetics
- Gene Expression Regulation, Developmental/drug effects
- Ghrelin/genetics
- Glucagon/genetics
- Homeodomain Proteins/genetics
- Insulin-Secreting Cells/drug effects*
- Insulin-Secreting Cells/physiology
- Polychlorinated Biphenyls/adverse effects*
- Trans-Activators/genetics
- Transcription Factors/genetics
- Zebrafish/embryology*
- Zebrafish Proteins/genetics
- PubMed
- 26393762 Full text @ Comp. Biochem. Physiol. C Toxicol. Pharmacol.
Citation
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.
Abstract
Exposures 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping