Aryl Hydrocarbon Receptor is Required for Prevention of Blood Clotting and for the Development of Vasculature and Bone in the Embryos of Medaka Fish, Oryzias latipes

The aryl hydrocarbon receptor (AHR) is a member of ligand-activated transcription factors and conserved among vertebrates. To investigate the role of AHR in fish development, medaka embryos were treated with agonist (2,3,7,8-tetrachlorodibenzo-p-dioxin), antagonists (alpha-naphthoflavone and resveratrol), and inhibitor (piperonyl butoxide) of cytochromes (Cyts) P450 encoded by a battery of target genes. These embryos were found to have similar abnormal phenotypes. Among the most consistent phenotypes were blood clotting and malformation of bone that were associated with vascular damages. These results thus indicate that control of AHR is important for proper development of fish embryos. AHR may control levels of Cyts P450 that are responsible for synthesis and metabolism of a toxic compound that caused the abnormal phenotypes. Complementary DNA fragments encoding AHR homologs were cloned from medaka embryos. AHR-specific mRNA was ubiquitously expressed in embryos and adult tissues.