Palatal abnormalities in the developing rat induced by retinoic acid

ABSTRACT

Palatogenesis is a complex developmental processthat requires two main events elevation andthen fusion of the palatal shelves. These processesare disrupted by teratogens such as retinoicacid (RA) and genetic defects, resulting in variousmalformations (including cleft palate). Usinghistological and immunohistochemical techniques,the effects of different isomers of RA, administeredin various concentrations to pregnantrats on different gestational days (GD), were assessedfrom observations of the state of palataldevelopment on GD 18 in foetuses without exencephaly.Varying degrees of clefting of thepalate were observed, from failure of elevationof the palatal shelves to failure of fusion in themidline. This study shows that all-trans-RA isthe most teratogenic RA isomer in terms of ratpalatal abnormalities. It also supports previousfindings that the timing of administration of alltrans-RA is more critical than the concentration,with treatment between GD 10 and 10.5 havingthe most severe effects. Previous histologicalstudies also suggested that RA is associatedwith the appearance of ectopic cartilages withinthe developing palate of foetuses showing exencephaly.In this investigation, immunohistochemicallabelling of the foetal material with antibodiesthat recognise epitopes present in linkproteins 1, 2, and 3 (8A4), chondroitin-4-sulphatestubs (2B6), and G1 and chondroitin sulphateattachments (7D1) present in aggrecan (associatedwith hyaluronan in cartilage) showedno signs of ectopic cartilage formation within the palate at GD18. Internal controls of the cartilagesof the nasal septum, vomeronasal cartilage, andMerkel’s cartilage labelled intensely and appearedmorphologically normal (AU)

RESUMEN

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