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Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity

Prarthana Shankar and Dan Villeneuve

No 38, OECD Series on Adverse Outcome Pathways from OECD Publishing

Abstract: The Aryl Hydrocarbon Receptors (Ahrs) are evolutionarily conserved ligand-dependent transcription factors that are activated by structurally diverse endogenous compounds as well as environmental chemicals such as polycyclic aromatic hydrocarbons and halogenated aromatic hydrocarbons. Ahr activation leads to several transcriptional changes that can cause developmental toxicity resulting in mortality. This AOP is part of a larger network of AOPs which describe how Ahr activation (molecular initiating event) can lead to early–life stage mortality (adverse outcome). The adverse outcome described in the AOP is cardiovascular toxicity via a decrease in the expression of SOX9, a protein that has been implicated in several functions such as in chondrogenesis, skeletal development, male gonad genesis, development of mesodermal tissues such as cardiac valves and septa, etc. This AOP is referred to as AOP 456 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki): https://aopwiki.org.

Date: 2025-06-26
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