In-plate toxicometabolomics of single zebrafish embryos
Journal article, 2020

Toxicometabolomic studies involving zebrafish embryos have become increasingly popular for linking apical endpoints to biochemical perturbations as part of adverse outcome pathway determination. These experiments involve pooling embryos to generate sufficient biomass for metabolomic measurement, which adds both time and cost. To address this limitation, we developed a high-throughput toxicometabolomic assay involving single zebrafish embryos. Incubation, microscopy, embryo extraction, and instrumental metabolomic analysis were all performed in the same 96-well plate, following acquisition of conventional toxicological endpoints. The total time for the assay (including testing of 6 doses/n= 12 embryos per dose plus positive and negative controls, assessing conventional endpoints, instrumental analysis, data processing and multivariate statistics) is <14 days. Metabolomic perturbations at low dose were linked statistically to those observed at high dose and in the presence of an adverse effect, thereby contextualizing omic data amongst apical endpoints. Overall, this assay enables collection of high resolution metabolomic data in a high throughput manner, suitable for mode of action hypothesis generation in the context of pharmaceutical or toxicological screening.

Author

Anton Ribbenstedt

Stockholm University

Malte Posselt

Stockholm University

Carl Brunius

Chalmers, Biology and Biological Engineering, Food and Nutrition Science

Jonathan P. Benskin

Stockholm University

Molecular Omics

25154184 (eISSN)

Vol. 16 3 185-194

Subject Categories

Aerospace Engineering

Biomedical Laboratory Science/Technology

Radiology, Nuclear Medicine and Medical Imaging

DOI

10.1039/d0mo00007h

PubMed

32191256

More information

Latest update

8/18/2020