The pathogenesis of retinoic acid-induced vertebral abnormalities in golden Syrian hamster fetuses.
Administration of single doses of retinoic acid to hamsters on days 7, 8, and 9 of pregnancy resulted in missing, irregular, and abnormally fused centers of ossification in the vertebrae of fetuses recovered near term. A study of early events in embryonic tissues following maternal treatment with 60 mg/kg of the teratogen on day 8 revealed a variety of changes which could be linked to the development of the bony defects. By 12 hours following treatment, the mean number of somites in teratogen-exposed embryos was significantly reduced in comparison to controls. Within 24 hours of maternal treatment, lesions were observed in the aortae of the retinoic acid-exposed embryos. The vessels were consistently damaged caudally with dissection of aortic contents into the adjacent unsegmented mesoderm. Kinking of the neural tube, notochordal irregularities, and a loss of intercellular relationships in the paraxial mesoderm accompanied the vascular lesions. By 36 hours following treatment, abnormalities were evident in the appearance of the caudal somites, and at later stages these appeared to translate into defects in the sclerotomes and subsequently, the vertebrae. The observations suggest that vascular damage plays a significant role in the induction of the vertebral defects by disrupting somitogenesis. Moreover, the results support the hypothesis that retinoic acid produces abnormalities in the vertebral skeleton by a mechanism different from that which has been suggested to operate in the induction of defects in the limb skeleton.
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D006224:Cricetinae / Q000196:embryology*; D005260:Female; D005865:Gestational Age; D008647:Mesocricetus / Q000196:embryology*; D008855:Microscopy, Electron, Scanning; D009672:Notochord / Q000648:ultrastructure; D011247:Pregnancy; D013131:Spine / Q000002:abnormalities* / Q000196:embryology; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin