Histological observations of palatal malformations in rat embryos induced by retinoic acid treatment

Malformations of the palate were induced in white rat embryos following mat ernal exposure to retinoic acid (tretinoin). Five experimental groups and t he controls were treated by the following protocol: Group 1: pregnant rats received 100 mg retinoic acid (RA)/kg b.w. suspended in corn oil on gestational day (GD) 11.5; Group 2: 20 mg RA/kg b.w. from G D 8-12; Group 3. 20 mg RA/kg b.w. from GD 7.5-11.5; Group 4. 100 mg RA/kg b .w. on GD 10-11; Group 5: 100 mg RA/kg b.w. on GD 10 and 12; Group 6 receiv ed corn oil vehicle from GD 7-14.5; and Group 6: served as non-injected con trols. In all retinoic acid treated groups, varying degrees of clefts with occasio nal attempts of fusion were noted. The severity and frequency of the malfor mations were dependent on dosage or gestational day of drug treatment. Our results indicate that RA, even at the lowest dose tested (20 mg/kg b.w.) se verely affects the various tissues constituting the embryonic palatal shelv es by altering cell interaction and possibly programmed cell death. These e vents would then result in lack of or inadequate differentiation with subse quent formation of aberrant craniofacial architecture.