Effects of Retinoic Acid on the Cell Proliferating Activity and the Expression of Fibroblast Growth Factor 2, Fibroblast Growth Factor Receptor 2 during Palatal Development of Mice / 대한해부학회지

ABSTRACT

Retinoic acid plays an important role in embryogenesis, by regulating morphogenesis, cell proliferation, differentiation, and extracellular matrix production. Also retinoic acid is a potent teratogen and induces a variety of limb and craniofacial malformations including cleft palate, that is the most common congenital malformation. Fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 2 (FGFR2) are an important role in the secondary induction for the epithelial-mesenchymal transformation during development. Mutations in them, produce a congenital malformation in the skeletal system and the craniofacial tissue. It was of interest to explore the hypothesis of an inhibitory effect exerted by retinoic acid on the cell proliferating activity and the expression of FGF2 and FGFR2 in the developing palate in vivo. In the present study, author observed the expression of PCNA as a marker for the cell proliferating activity, FGF2 and FGFR2 to compare with developmental stages and locations in normal and retinoic acid-induced cleft palate. Retinoic acid was administered orally at gestational day (GD) 10 to ICR mice. The pregnant mice were sacrificed on GD 12, 13, 14, 15 to obtain the fetuses. Scanning electron microscope and immunohistochemistry was performed. In the retinoic acid-treated fetuses, palatal shelves did not elevate and cleft palate was induced. On GD 12, 13 in the palatal mesenchyme of the retinoic acid treated-fetuses, expression of the PCNA decreased. On GD 12 in the palatal epithelium of the retinoic acid-treated fetuses, expression of FGFR2 decreased, but after GD 13, the patterns of expression of FGFR2 were not affected. On GD 12, 13 in the palatal epithelium and mesenchyme of the retinoic acid-treated fetuses, expression of FGF2 decreased dramatically, but after GD 14, it was similar to that in the normal fetal palate. These results suggest that retinoic acid inhibits the cell proliferating activity and the expression of FGF2, FGFR2 in the palatal mesenchyme on GD 12, 13, which is critical in the developing palate, and elevation of palatal shelves is delayed and impaired. Moreover, it seems that retinoic acid inhibits the epithelial-mesenchymal transformation of epithelium. Finally, cleft palate is induced.