Craniofacial and central nervous system malformations induced by triamcinolone acetonide in nonhuman primates: II. Craniofacial pathogenesis.
This study further defines the craniofacial malformations induced by triamcinolone acetonide in the rhesus monkey. Ten timed-mated pregnant rhesus monkeys (Macaca mulatta) received intramuscular injections of 10 mg/kg TAC on days 23, 25, 27, 29, and 31 of gestation. Results of previous experiments with rhesus and bonnet monkeys and baboons indicated that specific craniofacial and brain malformations could be induced with TAC during this period of pregnancy (Hendrickx et al., '80). Stage-matched TAC-treated and control embryos (stages 17-18 and 22) and age-matched TAC-treated and control fetuses (50, 60, and 70 days gestation) were removed by hysterotomy. Stage 17-18 TAC embryos appeared grossly normal but histologic evaluation revealed a shortened anlage of the posterior cranial base. Stage 22 TAC embryos and all TAC fetuses exhibited craniofacial dysmorphia and encephalocele. The developing sphenoid was the earliest affected and most severely malformed bone. Its defects included reduced anterioposterior and transverse dimensions, reduced orbitosphenoid and alisphenoid, abnormal pituitary fossa, and reduced dorsum and tuberculum sellae. In addition, shortening of the posterior cranial base and decreased cranial base angle was a consistent finding in the treated embryos and fetuses. Decreased ossification and remodeling in the facial bones and abnormal position due to the malformed sphenoid occurred.
D000818:Animals; D002490:Central Nervous System / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology; D005147:Facial Bones / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology; D005260:Female; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D008253:Macaca mulatta; D011247:Pregnancy; D012886:Skull / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology; D013723:Teratogens; D014222:Triamcinolone Acetonide / Q000633:toxicity*
D013723:Teratogens; D014222:Triamcinolone Acetonide