Effects of chlorcyclizine-induced glycosaminoglycan alterations on patterns of hyaluronate distribution during morphogenesis of the mouse secondary palate

Abstract

Chlorcyclizine (CHLR) enhances the degradation of hyaluronate (HA) into smaller molecular weight pieces with no effect on its synthesis. Administration of CHLR to pregnant CD-1 mice on gestational days 10.5, 11.5 and 12.5 results in 100% cleft palate in the fetuses. The caudal two thirds of the palatal shelves are reduced in size and unable to reorient in vitro, while anterior shelf regions are relatively unaffected. Alcian blue staining combined with specific enzymic digestion was used to identify HA in sections of CHLR-treated shelves. With the aid of computer-assisted image subtraction the patterns of HA distribution across the tissue section were objectively identified. Anterior, posterior and presumptive soft palatal shelf regions were examined at gestational days 13.25, 13.5, 13.75 and 14.5. Acquisition of a normal pattern of HA distribution was delayed by about 24 h, as compared to untreated specimens in all three shelf regions. The posterior and soft regions, comprising the caudal two thirds of the shelf, also showed pronounced shape change. These regions only displayed normal curvature of the nasal surface when a normal pattern of HA distribution was attained. These results suggest that, for the caudal two thirds of the palatal shelf, normal shape and the ability to remodel are linked to the molecular configuration of HA and to a specific pattern of HA distribution.