Refining adverse outcome pathways using Japanese Medaka Embryos (Oryzias latipes) exposed to 2,3,7,8-Tetrachlorodibenzodioxin

Abstract

Adverse outcome pathways (AOPs) are a framework that categorizes the impact of chemicals biologically from the initial molecular interaction through to the ecosystem level. This research aims to refine two existing AOPs that are initiated when dioxins and dioxin-like chemicals bind to molecular receptors. When embryonic development is adversely impacted by dioxins, we hypothesize that there are differences in gene and protein expression, which will distinguish the molecular level key events in these two AOPs. To test this, we performed qPCR on AOP key event genes, and also non-targeted proteomics on teleost embryos from different stages of development after exposure to dioxins and linked these to higher-level adverse effects, specifically cardiac impairment, and malformations. Refining these AOPs will benefit society by improving our ability to respond to chemical contaminants more effectively to prevent adverse outcomes in humans and their environment.