Zebrafish as a Biomedical Model to Define Developmental Origins of Chemical Toxicity

Abstract

Historically, toxicity studies have focused on an aligned exposure and assessment life period. In recent years, there are a growing number of studies evaluating potential adverse health outcomes in adult organisms that were exposed to a chemical only during a developmental stage. This exposure and assessment paradigm is commonly referred to as the “Developmental Origins of Health and Disease” or “DOHaD.” DOHaD studies have employed a variety of biological organisms in laboratory tests, including zebrafish. The zebrafish (Danio rerio) is a popular vertebrate model in developmental and molecular biology with growing adaptation in chemical toxicity studies. Most commonly, zebrafish have been used in developmental toxicity tests based on their strengths of high fecundity rates, ex vivo embryonic development, shorter developmental periods, and transparency, providing ease in the visualization of structures at the earliest developmental stages. In addition, high genetic homology and conservation of developmental processes and disease pathways enable translation to humans in these toxicity assessments. Furthermore, with their shorter life periods to maturation and aging, research using zebrafish for toxicity assessments throughout their lifespan are expanding, including within the DOHaD paradigm. In this chapter, studies employing the zebrafish to define mechanisms of toxicity using the DOHaD paradigm are discussed, providing connections between early-life chemical exposures and later-in-life adverse health outcomes.