title: Nitric oxide and teratogenesis: an update.
abstract: Nitric oxide (NO), generated by NO synthase (NOS) enzymes, is an important bioactive molecule involved in the regulation of several biological phenomena that are crucial for organogenesis, including gene expression, cell growth, matrix remolding, proliferation, differentiation and apoptosis. The expression of NOS isoforms in embryonic tissues is temporally and spatially regulated, and disruption of endogenous NO can lead to developmental defects. Maternal treatment with pan NOS inhibitors during early organogenesis caused severe malformations of the axial skeleton. In utero exposure during the fetal period induced limb reduction defects of vascular origin. Knock-out mice have been used to define the role of the various NOS isoforms on the origin of the abnormal development. Cardiovascular malformations, limb reduction defects, reduced growth and reduced survival have been observed in knock-out mice with targeted disruption of endothelial NOS (eNOS). Limited morphological changes were observed in mice lacking inducible NOS (iNOS) or neuronal NOS n(NOS). Results obtained with in vitro studies suggest that optimal levels of NO are required for neural tube closure. Disregulation of NO production was also recently proposed as a contributing mechanism in the origin of malformations associated with exposure to known environmental teratogens, such as valproic acid, thalidomide, copper deficiency, and diabetes.
authors: Gian Mario
authors: GM
authors: Tiboni
authors: Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini Chiet, Italy. tiboni@unich.it.
authors: Adalisa
authors: A
authors: Ponzano
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000633:toxicity; D005260:Female; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000009:adverse effects / Q000633:toxicity; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000201:enzymology; D064793:Teratogenesis / Q000187:drug effects* / Q000502:physiology; D013723:Teratogens / Q000633:toxicity
chemical_list: D004791:Enzyme Inhibitors; D013723:Teratogens; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester