Zebrafish as an integrative vertebrate model to identify miRNA mechanisms regulating toxicity

Abstract

Zebrafish (Danio rerio) are an integrative vertebrate model ideal for toxicity studies. The zebrafish genome is sequenced with detailed characterization of all life stages. With their genetic similarity to humans, zebrafish models are established to study biological processes including development and disease mechanisms for translation to human health. The zebrafish genome, similar to other eukaryotic organisms, contains microRNAs (miRNAs) which function along with other epigenetic mechanisms to regulate gene expression. Studies have now established that exposure to toxins and xenobiotics can change miRNA expression profiles resulting in various physiological and behavioral alterations. In this review, we cover the intersection of miRNA alterations from toxin or xenobiotic exposure with a focus on studies using the zebrafish model system to identify miRNA mechanisms regulating toxicity. Studies to date have addressed exposures to toxins, particulate matter and nanoparticles, various environmental contaminants including pesticides, ethanol, and pharmaceuticals. Current limitations of the completed studies and future directions for this research area are discussed.

Keywords: Epigenetics; Toxicology; Zebrafish; miRNA; microRNA.

Graphical abstract

Fig. 1

Zebrafish life cycle. Images are of an embryo at 1 h post fertilization (hpf), an eleutheroembryo at 5 days post fertilization (dpf), and adult female (top) and male (bottom) zebrafish.

Fig. 2

Total number of mature miRNAs currently identified in zebrafish, mouse, and human genomes. Numbers were attained from the latest version of miRbase release 22.1 (October 2018).