Emmanouil-Nikoloussi E N, Goret-Nicaise M, Foroglou P, Kerameos-Foroglou C, Persaud T V, Thliveris J A, Dhem A
Laboratory of Histology-Embryology, Faculty of Medicine, Aristotle University of Thessaloniki, Greece.
Exp Toxicol Pathol. 2000 Oct;52(5):437-44. doi: 10.1016/s0940-2993(00)80079-2.
Malformations of the palate were induced in white rat embryos following maternal exposure to retinoic acid (tretinoin). Five experimental groups and the 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 GD 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 received corn oil vehicle from GD 7-14.5; and Group 6: served as non-injected controls. In all retinoic acid treated groups, varying degrees of clefts with occasional attempts of fusion were noted. The severity and frequency of the malformations 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.) severely affects the various tissues constituting the embryonic palatal shelves by altering cell interaction and possibly programmed cell death. These events would then result in lack of or inadequate differentiation with subsequent formation of aberrant craniofacial architecture.
在母体接触视黄酸（维甲酸）后，白色大鼠胚胎中诱发了腭裂。五个实验组和对照组按以下方案进行处理：第1组：妊娠大鼠在妊娠第11.5天接受100毫克视黄酸（RA）/千克体重，悬浮于玉米油中；第2组：从妊娠第8天至12天给予20毫克RA/千克体重；第3组：从妊娠第7.5天至11.5天给予20毫克RA/千克体重；第4组：在妊娠第10天至11天给予100毫克RA/千克体重；第5组：在妊娠第10天和12天给予100毫克RA/千克体重；第6组从妊娠第7天至14.5天接受玉米油载体；第7组作为未注射的对照组。在所有视黄酸处理组中，均观察到不同程度的腭裂，偶尔有融合的尝试。畸形的严重程度和频率取决于药物治疗的剂量或妊娠天数。我们的结果表明，即使是测试的最低剂量（20毫克/千克体重）的RA，也会通过改变细胞相互作用以及可能的程序性细胞死亡，严重影响构成胚胎腭突的各种组织。这些事件随后会导致分化不足或缺乏，进而形成异常的颅面结构。
