Disturbances of palatogenesis and their prophylaxis in animal experiments

The goal of this study using experimental animals was to induce disturbances of palatogenesis which are comparable to human maxillary clefts. Simultaneously, an in vivo method of testing presumed antiteratogenic substances is presented. 13 gravid Wistar rats bearing 98 fetuses received 200 mg/kg of procarbazine on day 14 post conception (p. c.) to induce malformations. 7 of these gravid animals, bearing 48 fetuses, additionally received 200 mg/kg thiamine daily from day 13-19 p. c. to prevent malformations. On day 20 p. c., the fetuses were teratologically screened: all fetuses were externally examined, the skeletons of 1/3 were visualized using cartilage/bone staining methods, and the heads of 2/3 were histologically examined in 24 sequential frontal sections. At birth, the procarbazine-damaged fetuses exhibited a high rate of cleft palate, primarily involving the secondary palate (94%), which was accompanied by retardation and delayed ossification of the viscerocranium. 66% of the fetuses showed pronounced brachygenia. The disturbances of palatogenesis were frequently accompanied by disturbed odontogenesis, which chiefly manifested itself near the cleft of the frontal maxilla as a reduction in size (63%), retardation (38%) or absence (31%) of the tooth germ. In the trial group additionally treated with thiamine, the findings did not differ significantly from these. The animal model presented here proved suitable for studying palatogenesis and localization-specific testing of substances presumed to have antiteratogenic effects. A prophylactic effect of thiamine initially tested as a highly-dosed monotherapy was not verifiable.