Effects of all-trans retinoic acid on palatal fusion and its molecular mechanisms.

Objective To investigate the effect of excessive all-trans retinoic acid (atRA) on mouse embryonic palatal fusion and the mechanism. Method Palatal shelves from embryonic D 13 embryonic mice were cultured in BGJb medium and treated with vehicle control only or 5 μmol/L atRA for 72 h. Palatal fusion was examined by hemagglutinin esterase. Apoptosis and laminin were detected by TUNEL and immunohistochemistry, respectively. The level of Smad2 phosphorylation (pSmad2) was analyzed by Western blot. Results atRA led to failure of palatal fusion and inhibited the migration and apoptosis of medial edge epithelial cells (MEE) and degradation of basal lamina within, compared with control palatal shelves in cultures. Additionally, apoptosis was detected in mesenchyme of atRA-treated palatal shelves. Further experiment revealed that pSmad2 was abrogated by atRA. Conclusion atRA induced failure of palatal fusion through inhibition of apoptosis of the MEE cell and degradation of basal lamina within medial edge epithelial seam. Inhibition of pSmad2 may account for the failure of palatal fusion by atRA.