Adverse Outcome Pathway on aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX‑2

This AOP details the linkage between activation of the aryl hydrocarbon receptor (AhR) and early life stage mortality in oviparous vertebrates. It can be initiated mostly by dioxin-like compounds, which are able to bind to the AhR causing heterodimerisation with the aryl hydrocarbon nuclear translocator (ARNT) and interaction with dioxin-responsive elements on the DNA causing an up-regulation in dioxin responsive genes. One dioxin-responsive gene is cyclooxygenase 2 (COX-2), which has roles in development of the cardiovascular system. Up-regulation in expression of COX-2 causes alteration in cardiovascular development and function resulting in reduced heart pumping efficiency, reduced blood flow, and eventual cardiac collapse and death. Comparable apical manifestations of activation of the AhR have been recorded across freshwater and marine teleost and non-teleost fishes, as well as birds. Despite conservation in the AOP across taxa, great differences in sensitivity to perturbation exist both among and within taxonomic groups.