Immediate and long-term consequences of vascular toxicity during zebrafish development

Tal, Tamara; McCollum, Catherine W.; Harris, Peggy S.; Olin, Jeanene K.; Kleinstreuer, Nicole; Wood, Charles E.; Hans, Charu; Shah, Shishir K.; Merchant, Fatima A.; Bondesson, Maria; Knudsen, Thomas B.; Padilla, Stephanie; Hemmer, Michael J.

doi:10.1016/j.reprotox.2014.05.014

Cited by 25 publications

(24 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, the pVDC test set was assessed in Tg(kdrl:EGFP) embryos exposed to test chemicals from 26–72 hpf and assessed for abnormal angiogenic development at 72 hpf (Figure 3A and [9]). In comparison to vehicle control larvae (Figure 3B), seven positives were identified: 1-hydroxypyrene and haloperidol (Figure 3C) and disulfiram, fluazinam, pyridaben, tert-butylhydroquinone, and triclocarban (Supplemental Figure S3).…”

Section: Resultsmentioning

confidence: 99%

“…Based on previous methods [9], bleached embryos were housed in 100 mm Petri dishes at 26°C overnight. At 24 hpf, embryos were enzymatically or manually dechorionated and statically exposed to test compounds from 26–72 hours post fertilization (hpf) in glass 96 well plates containing 500 μl of test chemical in 10% Hanks’ balanced salt solution [22] at a final concentration of 0.4% DMSO.…”

Section: Methodsmentioning

confidence: 99%

“…Despite these observations, data concerning chemical-target interactions underlying developmental vascular toxicity is limited. Previous studies have explored this issue utilizing experimental and computational models based on in vitro data from high-throughput screening (HTS) assays [2; 6; 7; 8; 9]. A multi-tiered approach, involving the integration of in vitro data with in silico models and in vivo apical endpoints is necessary to build insight into how chemical disruption of vascular development might ultimately lead to adverse outcomes.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

Tal

Kilty

Smith

et al. 2017

Reproductive Toxicology

View full text Add to dashboard Cite

Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive pVDC signature was constructed from 124 U.S. EPA ToxCast high-throughput screening (HTS) assays and used to rank 1060 chemicals for their potential to disrupt vascular development. Thirty-seven compounds were selected for targeted testing in transgenic Tg(kdrl:EGFP) and Tg(fli1:EGFP) zebrafish embryos to identify chemicals that impair developmental angiogenesis. We hypothesized that zebrafish angiogenesis toxicity data would correlate with human cell-based and cell-free in vitro HTS ToxCast data. Univariate statistical associations used to filter HTS data based on correlations with zebrafish angiogenic inhibition in vivo revealed 132 total significant associations, 33 of which were already captured in the pVDC signature, and 689 non-significant assay associations. Correlated assays were enriched in cytokine and extracellular matrix pathways. Taken together, the findings indicate the utility of zebrafish assays to evaluate an HTS-based predictive toxicity signature and also provide an experimental basis for expansion of the pVDC signature with novel HTS assays.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

Tal

Kilty

Smith

et al. 2017

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

“…Use of zebrafish as a tool for screening genetic mutations and toxicants on vascular development has prompted the development of high throughput image analysis approaches for quantifying the vasculature [ 8,9,11,20]. Though these reported analysis frameworks often give excellent visual representations of the analysis they can be in practice hard to implement or adjust due to the necessity to use programming languages such as C++ [ 8].…”

Section: Discussionmentioning

confidence: 99%

“…Though these reported analysis frameworks often give excellent visual representations of the analysis they can be in practice hard to implement or adjust due to the necessity to use programming languages such as C++ [ 8]. Some methods use microscopy software to assist with manually measuring the lengths of the vessels [ 20] and such methods which focus on ISV vessel lengths did not generate data on vessel junctions and hence give no indication of vessel connectivity [ 9]. The strategy described in this study is not fully automated and requires user input to select the region or vessels to be analysed; however the image processing was then relatively quick with each image analysed in less than 1 minute and generating an output which can be manipulated to give the parameters of interest.…”

Section: Discussionmentioning

confidence: 99%

Development of an ImageJ-based method for analysing the developing zebrafish vasculature

Simms

Bicknell²,

Heath

2017

Vasc Cell

View full text Add to dashboard Cite

Zebrafish with fluorescently labelled blood vessels provide an excellent model for studying angiogenesis. Most commonly the growth of the intersegmental blood vessels is investigated in response to compounds or manipulation of gene expression and analysed using manual methods, typically scoring the connectivity of these blood vessels to the dorsal longitudinal anastomotic vessel. Such methods are laborious and best suited to time points after the connectivity of these vessels has been established. By contrast, reported image processing-based methods are difficult to implement and often depend on specialist software. This study aimed to develop and evaluate a computational method using the freely available ImageJ software to quantify the development of intersegmental blood vessel formation. This methodology enabled rapid analysis of vascular development. The outputs of total vessel length and number of junctions best documented defective vascular development at differing levels of severity and gave comparable results to the frequently used manual approach of calculating the percentage connectivity of the intersegmental vessels. This ImageJ-based analysis method allowed objective quantitation of vascular network formation in zebrafish enabling a free, straightforward and rapid approach to determine the effect of novel compounds or genetic manipulation of the angiogenic process. Keywords Zebrafish -angiogenesis -vessel quantitation IntroductionThe zebrafish ( Danio rerio) is a powerful and widely used model organism for the study of vascular development and angiogenesis. Features such as the embryo's rapid and external development, small size, optical transparency, fluorescent tagging of vessels and methods to modify its gene expression all contribute to its utility in studying vessel development [ 1]. This vertebrate model shares both anatomical features and similar molecular mechanisms of vessel development observed in higher vertebrates making this a valuable tool for understanding gene function in both normal human development and angiogenesis dependent pathologies [ 2,3].The widespread use of zebrafish in studying the effects of genes or compounds in vessel development were used in conjunction with confocal fluorescence microscopy to generate high resolution vascular images, which were then subjected to processing and analysis using the Analyze Skeleton 2D/3D plugin of ImageJ. This computational analysis method was tested by using images generated via a developmental time course as well as images of embryos with varying levels of vascular disruption produced either pharmacologically or by translation blocking morpholino oligonucleotides. Of the generated analysis outputs, total vessel length and junction number best allowed differentiation between the varying phenotypes. This method allowed objective quantitation of vascular network formation in zebrafish enabling a more rapid and systematic approach to determine the effect of novel compounds or genetic manipulation of the angiogenic process. Methods Z...

show abstract

Vasculotoxicity of Metal‐Based Nanoparticles

Sepúlveda

Gao

2022

Toxicology of Nanoparticles and Nanomaterials in Human, Terrestrial and Aquatic Systems

View full text Add to dashboard Cite

Immediate and long-term consequences of vascular toxicity during zebrafish development

Cited by 25 publications

References 50 publications

Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

Development of an ImageJ-based method for analysing the developing zebrafish vasculature

Vasculotoxicity of Metal‐Based Nanoparticles

Contact Info

Product

Resources

About