Comparison of cleft palate induction by Nicotiana glauca in goats and sheep

The induction of cleft palate by Nicotiana glauca (wild tree tobacco) durin g the first trimester of pregnancy was compared between Spanish-type goats and crossbred western-type sheep. Cleft palate was induced in 100% of the e mbryonic/fetal goats when their pregnant mothers were gavaged with N. glauc a plant material or with anabasine-rich extracts from the latter, during ge station days 32-41. Seventy-five percent of newborn goats had cleft palate after maternal dosing with N. glauca during gestation days 35-41, while no cleft palates were induced when dosing periods included days 36-40, 37-39, or day 38 only. The induced cleft palates were bilateral, involving the ent ire secondary palates with complete detachment of the vomer. Eleven percent of the newborn goats from does gavaged during gestation days 32-41 had ext racranial abnormalities, most often contractures of the metacarpal joints. Most of these contractures resolved spontaneously by 4-6 weeks postpartum. One new-born kid also had an asymmetric skull due to apparent fetal positio ning. No cleft palates were induced in lambs whose mothers were gavaged wit h N. glauca plant or anabasine-rich extracts during gestation days 34-41, 3 5-40, 35-41, 36-41, 35-51, or 37-50. Only one of five lambs born to three e wes gavaged with N. glauca plant material during gestation days 34-55 had a cleft palate, but all five of these lambs had moderate to severe contractu res in the metacarpal joints. The slight to moderate contracture defects re solved spontaneously by 4-6 weeks postpartum, but the severe contractures r esolved only partially. Embryonic/fetal death and resorption (determined by ultrasound) occurred in 25% of pregnant goats fed N, glauca compared to on ly 4% of pregnant sheep. Nicotiana glauca plant material contained the tera togenic alkaloid anabasine at 0.175% to 0.23%, dry weight, demonstrating th at Spanish-type goats are susceptible to cleft palate induction by the natu ral toxin anabasine, while crossbred western-type sheep are resistant. Howe ver, clinical signs of toxicity were equally severe in goats and sheep, eve n though maternal alkaloid tolerance was generally lower in sheep. We postu late that an alkaloid-induced reduction in fetal movement during the period of normal palate closure is the cause of the cleft palate and multiple fle xion contractures. Published 2000 Wiley-Liss, Inc.