PATHOGENESIS OF CRANIOFACIAL AND BODY-WALL MALFORMATIONS INDUCED BY OCHRATOXIN-A IN MICE

Ochratoxin A (OA), a mycotoxin commonly found in soils and on moldy fo od such as cereal grains, is a potent teratogen. The present investiga tion was designed to examine the teratogenicity of OA administered acu tely at early post-implantation stages in mice, with particular emphas is on the pathogenetic basis of induced malformations. Maternal OA adm inistration on gestational day (GD) 7 or 8 resulted in excessive amoun ts of cell death in selected cell populations. After a single dose of 2-4 mg/kg, excessive cell death was notable within 6 hours, and persis ted to 36 hours post-treatment. As observed in GD 14 or 18 fetuses, th e spectrum of induced craniofacial malformations included exencephaly, midfacial clefting, cleft lip, as well as hypotelorism, and synophtha lmia associated with holoprosencephaly. Body wall defects involved eit her the abdominal wall alone, or in combination with the thoracic wall , resulting in partial or complete exposure of the viscera. Potential mechanisms for OA-induced selective cell killing are discussed. (C) 19 93 Wiley-Liss, Inc.