TY  - JOUR
A1  - ,  
T1  - Palatal abnormalities in the developing rat induced by retinoic acid
JO  - Eur. J. Anat.
SN  - 1136-4890
Y1  - 2005
VL  - 9
SP  - 1
EP  - 16
UR  - http://www.eurjanat.com/web/paper.php?id=05010001
KW  - aggrecan
KW  - chondroitin 4 sulfate
KW  - chondroitin sulfate
KW  - epitope
KW  - etretin
KW  - hyaluronic acid
KW  - isotretinoin
KW  - link protein
KW  - retinoic acid
KW  - teratogenic agent
KW  - animal experiment
KW  - animal model
KW  - animal tissue
KW  - article
KW  - cartilage
KW  - cleft palate
KW  - concentration response
KW  - controlled study
KW  - craniofacial development
KW  - drug effect
KW  - ectopic tissue
KW  - exencephaly
KW  - female
KW  - fetus
KW  - gestational age
KW  - histopathology
KW  - immunohistochemistry
KW  - isomer
KW  - nonhuman
KW  - nose septum
KW  - palate malformation
KW  - rat
KW  - rat strain
KW  - teratogenicity
KW  - vomeronasal organ
N2  - Palatogenesis is a complex developmental process that requires two main events: elevation and then fusion of the palatal shelves. These processes are disrupted by teratogens such as retinoic acid (RA) and genetic defects, resulting in various malformations (including cleft palate). Using histological and immunohistochemical techniques, the effects of different isomers of RA, administered in various concentrations to pregnant rats on different gestational days (GD), were assessed from observations of the state of palatal development on GD 18 in foetuses without exencephaly. Varying degrees of clefting of the palate were observed, from failure of elevation of the palatal shelves to failure of fusion in the midline. This study shows that all-trans-RA is the most teratogenic RA isomer in terms of rat palatal abnormalities. It also supports previous findings that the timing of administration of all-trans-RA is more critical than the concentration, with treatment between GD 10 and 10.5 having the most severe effects. Previous histological studies also suggested that RA is associated with the appearance of ectopic cartilages within the developing palate of foetuses showing exencephaly. In this investigation, immunohistochemical labelling of the foetal material with antibodies that recognise epitopes present in link proteins 1, 2, and 3 (8A4), chondroitin-4-sulphate stubs (2B6), and G1 and chondroitin sulphate attachments (7D1) present in aggrecan (associated with hyaluronan in cartilage) showed no signs of ectopic cartilage formation within the palate at GD18. Internal controls of the cartilages of the nasal septum, vomeronasal cartilage, and Merkel's cartilage labelled intensely and appeared morphologically normal.
ER  -