Role of nitric oxide in chick embryonic organogenesis and dysmorphogenesis

✍ Scribed by Peter G. Alexander; Lillian Chau; Rocky S. Tuan

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 417 KB
• Volume: 79
• Category: Article
• ISSN: 1542-0752
• DOI: 10.1002/bdra.20386

✦ Synopsis

Abstract

BACKGROUND: Nitric oxide (NO), produced by the nitric oxide synthase family of enzymes, mediates multiple signaling functions, and when unchecked, NO causes pathological damage. Exposure of embryos to a variety of teratogens, including carbon monoxide (CO), has been shown to increase reactive intermediates, such as NO, and recent work showed that either the excess or absence of NO caused morphological defects. While endogenous NO is known to regulate many adult tissues, its role during embryonic organogenesis and/or in mediating responses to teratogen exposure has not been explored. METHODS: We have examined here the presence of NO during normal chick embryonic organogenesis, and investigated the teratogenicity of NO through the application of sodium nitroprusside (SNP), which mimics NO overproduction, and NG‐monomethyl‐L‐arginine (L‐NMMA), which inhibits endogenous NOS activity. RESULTS: Topical treatment with SNP or L‐NMMA for 18 h resulted in morphological defects, specifically in the neural tube and somites, which corresponded to sites of altered apoptosis. The location of NO was histochemically correlated with the observed morphological defects. Coadministration of SNP or L‐NMMA with CO showed functional coregulation and interaction between NO and CO in chick embryonic development. CONCLUSIONS: Our results showed that regulation of NO is essential for normal axial development, that sites of altered NO expression correlate to those of altered apoptosis and dysmorphogenesis, and that CO coadministration resulted in a rectification of normal NO expression. Collectively, these results suggest that alteration in endogenous NO/CO signaling is responsible, at least in part, for the observed NO‐induced teratogenesis. © 2007 Wiley‐Liss, Inc.