Involvement of apoptotic cell death and cell cycle perturbation in retinoic acid-induced cleft palate in mice
- Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501 (Japan) and Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Kyoto (Japan)
- Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501 (Japan)
Retinoic acid (RA), a metabolite of vitamin A, plays a key role in a variety of biological processes and is essential for normal embryonic development. On the other hand, exogenous RA could cause cleft palate in offspring when it is given to pregnant animals at either the early or late phases of palatogenesis, but the pathogenetic mechanism of cleft palate caused by excess RA remains not fully elucidated. The aim of the present study was to investigate the effects of excess of RA on early palatogenesis in mouse fetuses and analyze the teratogenic mechanism, especially at the stage prior to palatal shelf elevation. We gave all-trans RA (100 mg/kg) orally to E11.5 ICR pregnant mice and observed the changes occurring in the palatal shelves of their fetuses. It was found that apoptotic cell death increased not only in the epithelium of the palatal shelves but also in the tongue primordium, which might affect tongue withdrawal movement during palatogenesis and impair the horizontal elevation of palatal shelves. In addition, RA was found to prevent the G{sub 1}/S progression of palatal mesenchymal cells through upregulation of p21 {sup Cip1}, leading to Rb hypophospholylation. Thus, RA appears to cause G{sub 1} arrest in palatal mesenchymal cells in a similar manner as in various cancer and embryonic cells. It is likely that apoptotic cell death and cell cycle disruption are involved in cleft palate formation induced by RA.
- OSTI ID:
- 20976933
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 221, Issue 1; Other Information: DOI: 10.1016/j.taap.2007.02.019; PII: S0041-008X(07)00084-1; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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