The morphogenesis of beta-aminopropionitrile-induced rib malformation in fetal golden Syrian hamsters.
In order to provide information on the mechanism of beta-aminopropionitrile (betaapn) induced teratogenesis, the pathogenesis of a fetal rib abnormality was studied at relatively short time intervals following maternal treatment with 2,500 mg/kg aqueous betaapn on day 11 of gestation. Histochemical tests of ribs from betaapn-exposed fetuses indicated a slight decrease in the level of glycosaminoglycans but at a time when the defect was already morphologically established. Ultrastructural observations on the chondrocytes of ribs from betaapn-exposed fetuses revealed alterations in mitochondrial structure indicative of a slight cytotoxic effect for the teratogen. The mitochondrial changes were transient, occurring initially at three hours after treatment and lasting for nine hours. Alterations in the size of collagen fibres in the cartilage of the fetal rib were also observed in the offspring of betaapn treated females. The mean diameter of collagen fibres in the ribs of control fetuses increased throughout the course of the study. The mean diameter of fibres in the fetuses of betaapn-exposed females failed to show any increase and was found to be significantly less than controls as early as three hours following maternal administration. The results suggested that the principal factor in the production of the fetal rib deformity was fundamentally the same as that known to affect the adult; namely a defect in the extracellular maturation of collagen.
D000014:Abnormalities, Drug-Induced; D000629:Aminopropionitrile / Q000494:pharmacology*; D000818:Animals; D002356:Cartilage / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D005865:Gestational Age; D006025:Glycosaminoglycans / Q000378:metabolism; D006651:Histocytochemistry; D008928:Mitochondria / Q000648:ultrastructure; D008968:Molecular Conformation; D011247:Pregnancy; D012272:Ribs / Q000002:abnormalities* / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors
D006025:Glycosaminoglycans; D000629:Aminopropionitrile; D003094:Collagen