<原著>CL/Frマウスの自然発現口唇口蓋裂の形態学的研究およびビタミンAの奇形発現予防作用
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概要
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To clarify the occurrence and prevention of cleft lip and palate (CLP) in humans, CL/Fr mice, which are a spontaneous CLP animal model, were investigated from morphologic and embryologic standpoints. At first, visceral and skeletal observations, craniofacial measurement and orofacial observations with special reference to the relationship between types of CLP and development of palatal shelves were perfomed on day 18 fetuses. The body weight and ossifications were not different between CLP (+) and (-) fetuses and major visceral abnormalities were not found in either CLP (+) or (-) fetuses. The incidence of CLP was 28.4% and several types of CLP similar to humans were noted. Most of the CLP were bilateral complete (61.0%) followed by left complete (16.9%). Severer CLP, such as complete CLP, had wider cleft of the secondary palate and more poorly developed palatal shelves. Craniofacial measurement showed that CLP (+) fetuses had shorter head height, shorter face height, wider palatal width and shorter mandibular length compared to CLP (-). Secondly, palatal shelves were cultured for 96 and 72 hours in serum free medium from day 12 and day 13 of gestation, respectively. The development of palatal shelves in vitro was less advanced in CL/Fr mice than ICR mice regardless of existence of non-existence of cleft lip (CL) before culture. The degree of inhibition was more extensive in CL (+) mice than CL (-) mice. The palatal region itself in the CL/Fr mice was suggested to be liable to become cleft palate (CP). Furthermore, the development of palatal shelves in CL (+) mice in vitro, in which situation maternal factors as well as neighboring organs such as brain, mandible and tongue are removed, tended to be better than in vivo. Thirdly, to examine the effect of vitamin A (VA) on the occurrence of CLP, VA (Chocola A, EISAI) was intraperitoneally given at a dose of 50,150 and 450 IU/g to pregnant CL/Fr mice on day 10 of gestation. The incidences of CLP in vivo from the autopsy of day 16 fetuses and the development of palatal shelves at 72 hours of culture from day 13 of gestation were examined. The incidence of CL in vivo after VA treatment tended to decrease compared to the controls (saline treatment). In the 450 IU/g VA group, late embryonic death and external abnormalities (CP, micrognathia, micromelia and digital anomalies) increased significantly compared to the controls. The development of palatal shelves in vitro were more advanced, especially in the 150 IU/g VA group, than the controls regardless of the existence or non-existence of CL. Therefore, VA was considered to have an optimum dose to decrease the incidence of CLP in CL/Fr mice and this strain may be VA deficient. The present study suggests that CLP can be prevented by external factors such as VA. To explore these findings to humans, further studies both in vivo and in vitro are necessary, and the biochemical supports to clarify whether the preventive effect is due to the primary effect of VA itself on the orofacial region or is a secondary effect through maternal and/or fetal modifications.
- 近畿大学の論文
- 1995-06-25