Omics in Zebrafish Teratogenesis

Abstract

The genome revolution represents a complete change on our view of biological systems. The quantitative determination of changes in all major molecular components of the living cells, the "omics" approach, opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics, and others, together with appropriate prediction and modeling tools, will mark the future of developmental toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology, which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement. Rodents and frogs have been the favorite models for studying human reproductive and developmental disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system to analyze in vivo developmental alterations that only can be studied applying in toto approaches. Moreover, under actual legislations, ZE is considered as a replacement model (and therefore, excluded from animal welfare regulations) during the first 5 days after fertilization. Here we review the most important components of the zebrafish toolbox available for analyzing early stages of embryotoxic events that could eventually lead to teratogenesis.

Zebrafish as a model for studing extracellular vesicles.

“…В последнее десятилетие рыбы Danio rerio стали широко использоваться в качестве модельного организма для изучения молекулярных механизмов развития и течения различных патофизиологических состояний, для оценки эффективности терапевтических агентов и поиска новых терапевтических подходов. По сравнению с лабораторными млекопитающими животными, такими как крысы, мыши, кролики, рыбы обладают рядом преимуществ: высоким уровнем фертильности; большим количеством особей в потомстве (50-200); коротким периодом эмбриогенеза (большинство органов, включая нервную систему, сердечно-сосудистую систему, кишечник, печень и почки, дифференцируются и функционируют уже через 5 дней после оплодотворения); высоким содержанием белков (около 70 %) и генов-ортологов (около 47 %) с Homo sapiens; а также простотой и экономичностью в содержании и разведении [1]. Zebrafish обладают сходством органов и тканей на анатомическом, физиологическом и молекулярном уровнях с их аналогами у млекопитающих [2].…”

Identification of proteome markers for drug-induced liver injury in zebrafish embryos

“…Proteomics analysis is an additional tool, which is already routinely applied on patient serum for diagnosis, and this can also be used to generate better understanding of the underlying molecular mechanisms of hepatotoxicity, while it provides quantitative information of molecular events at a more functional level (Kralj et al, 2021). Proteomics has been applied in the zebrafish embryo, albeit mainly targeted at unraveling developmental processes (Pina et al, 2018;Purushothaman et al, 2019). The objective of this study was to identify proteomic signatures which mark hepatotoxic events in the zebrafish embryo.…”

Genetic Susceptibility to Drug Teratogenicity: A Systematic Literature Review

“…Although little was known about gene-environment interactions and developmental processes at the time Wilson formulated his principles, recent advances in genetics and developmental biology have led to significant improvements in our understanding of the mechanisms of teratogenesis (Yalcin et al, 2015 ; Griffiths et al, 2018 ; Piña et al, 2018 ). Teratogenic events are complex, but an examination of genetic influences on drug response (pharmacogenetics) may promote our understanding of the molecular mechanisms involved (Cassina et al, 2012 ).…”