PUBLICATION
            Ioxynil and diethylstilbestrol disrupt vascular and heart development in zebrafish
- Authors
 - Li, Y.F., Canário, A.V.M., Power, D.M., Campinho, M.A.
 - ID
 - ZDB-PUB-190128-3
 - Date
 - 2019
 - Source
 - Environment International 124: 511-520 (Journal)
 - Registered Authors
 - Campinho, Marco António
 - Keywords
 - none
 - MeSH Terms
 - 
    
        
        
            
                
- Diethylstilbestrol/toxicity*
 - Endocrine System/drug effects
 - Water Pollutants, Chemical/toxicity
 - Cardiovascular System/drug effects*
 - Cardiovascular System/embryology*
 - Iodobenzenes/toxicity
 - Animals
 - Nitriles/toxicity*
 - Thyroid Gland/drug effects
 - Endocrine Disruptors/toxicity*
 - Embryo, Nonmammalian/drug effects*
 - Zebrafish/embryology
 
 - PubMed
 - 30685453 Full text @ Environ. Int.
 
            Citation
        
        
            Li, Y.F., Canário, A.V.M., Power, D.M., Campinho, M.A. (2019) Ioxynil and diethylstilbestrol disrupt vascular and heart development in zebrafish. Environment International. 124:511-520.
        
    
                
                    
                        Abstract
                    
                    
                
                
            
        
        
    
        
            
            
 
    
    
        
    
Background Endocrine disruption is one of the consequences of industrialization and chemicals released into the environment have a profound impact on organisms. Waterborne micromolar concentrations of ioxynil (IOX) and diethylstilbestrol (DES) in fish affect the development of the heart, vasculature and thyroid gland.
Objectives The present study aimed to determine how IOX and DES disrupt the crosstalk between the developing thyroid gland and cardio-vascular system in zebrafish.
Methods Twelve hours post fertilization (hpf) wild type, Tg(fli1:GFP) or Tg(cmalc2:GFPCaaX) zebrafish embryos were exposed to 0.1 μM IOX or DES for 36 h (up until 48 hpf) or 60 h (up until 72 hpf). Embryos were used for vascular endothelial cell sorting, whole-mount immunohistochemistry, tissue selective transcriptomics, selected gene expression analysis by quantitative real-time polymerase chain reaction analysis and determination of heart rate by live imaging.
Results Exposure of zebrafish embryos to IOX and DES (0.1 μM) increased heart beat frequency and reduced ventricle volume and aorta diameter. The transcriptome of endothelial cells from blood vessels of hypertrophic, dilated and arrhythmogenic right ventricular cardiomyopathy was significantly changed and compound-specific toxic effects were found in IOX and DES exposed embryos. Both DES and IOX directly affected vascular and heart development and this indirectly impaired thyroid gland development in zebrafish. Even though the toxicity end-point of the two chemicals was similar, their action seemed to be via different gene regulatory pathways and physiological mechanisms.
Conclusion IOX and DES directly disrupt cardiovascular development and there is an associated disruption of thyroid tissue that most likely has long term consequences for this endocrine axis.
            
    
                
                    
                        Genes / Markers
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Expression
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Phenotype
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Mutations / Transgenics
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Human Disease / Model
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Sequence Targeting Reagents
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Fish
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Orthology
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Engineered Foreign Genes
                    
                    
                
                
            
        
        
    
        
            
            
        
        
    
    
    
                
                    
                        Mapping