Submitted to: Teratology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/20/1999
Publication Date: 6/1/2000
Citation: PANTER, K.E., WEINZWEIG, J., GARDNER, D.R., STEGELMEIER, B.L., JAMES, L.F. COMPARISON OF CLEFT PALATE INDUCTION BY NICOTIANA GLAUCA IN FETAL GOATS AND SHEEP. TERATOLOGY. 2000. Interpretive Summary: Cleft palate was induced in fetal goats when their mothers were fed wild tree tobacco (Nicotiana glauca) during 32-41 days of pregnancy. Ninety seven percent of the fetal goats had cleft palate,14% had other abnormal craniofacial defects in addition to cleft palates and 11% had moderate to severe contracture skeletal defects. In contrast, less than 3% of newborn lambs had cleft palate when their pregnant mothers were fed wild tree tobacco and extracts therefrom during similar but extended stages of pregnancy including 34 to 55 days. Moderate to severe contractures occurred in newborn lambs when their mothers were fed wild tree tobacco during 34-55 days of pregnancy. The goat has now been characterized as a model to study the cause of cleft palate in livestock and humans and to develop techniques for potential in utero scarless repair.
Technical Abstract: Fetal cleft palate by maternal gavage of Nicotiana glauca during the first trimester of pregnancy was compared between goats and sheep. Cleft palate was induced in over 97% of the fetal goats when their pregnant mothers were fed N. glauca plant material or anabasine-rich extracts therefrom during gestation days 35-41, while no cleft palates were induced when feeding periods included days 36-40, 37-39 or day 38 only. The induced cleft palates were bilateral, involving the entire secondary palates with complete detachment of the vomer. In addition to cleft palates, 14% of the newborn kids showed other abnormal craniofacial defects including maxillary hypoplasia, midfacial retrusion and malocclusion. Eleven percent (3/26) or the newborn goats from dose fed during gestation days 32-41 had moderate to severe contractures of the metacarpal joints which resolved spontaneously by 4 weeks postpartum. There were no other gross malformations. No cleft palates were induced in lambs whose mothers were fed N. glauca plant or anabasine-rich extracts during the gestation periods of days 34-41, 35-40, 35-41, 36-41, 35-51 or 37-50. Only one of five lambs born to three ewes fed N. glauca plant material during gestation days 34-55 had a cleft palate, but all five lambs had moderate to severe contractures in the metacarpal joints. The slight to moderate contracture defects resolved spontaneously by 4 weeks postpartum, but the severe contractures only partially resolved. Fetal death and resorption (determined by ultrasound) occurred in 25% of pregnant goats fed N. glauca versus only 4% of pregnant sheep. Nicotiana glauca plant material contained the teratogenic alkaloid anabasine at 0.175% to 0.23% dry weight.