The fetal cleft palate: v. elucidation of the mechanism of palatal clefting in the congenital caprine model.
BACKGROUND
Failure of palatal shelf fusion at the precise gestational time point when shelf elevation and migration normally occur results in clefting. The present study defined the mechanism of clefting in the congenital caprine model by evaluating the temporal sequence of palatal shelf fusion.


METHODS
Six Spanish-type goats pregnant with twins were gavaged for 10 days (gestational days 32 to 41) with anabasine. Goats were examined with ultrasound throughout this period to assess fetal movement and evaluated histologically. Twelve untreated, unclefted fetuses served as controls.


RESULTS
After anabasine induction, real-time ultrasound confirmed a dramatic decrease in fetal movement. Hyperflexion of the neck occurred throughout the experimental period compared with control fetuses, in which spontaneous neck movements occurred. Histologic evaluation of the induced fetuses demonstrated the tongue wedged between the palatal shelves throughout the period of fusion. The shelves remained vertically oriented without elevation, ultimately resulting in clefting. The unclefted, control group demonstrated progressive elevation and migration of the palatal shelves between gestational days 38 and 40, with contact and fusion of the medial edge epithelia in the midline.


CONCLUSIONS
Palatal clefting in the congenital caprine model occurred concomitant with reduced fetal movement. Resultant neck hyperflexion causes the tongue to obstruct medial migration of the palatal shelves and fusion, whereas the shelves themselves are either directly prevented from elevation secondary to anabasine impairment or indirectly secondary to the obstructing tongue. Although the molecular mechanism for the teratogenic effects of anabasine remains elusive, the authors have demonstrated an association between reduced fetal movement and palatal clefting in their congenital caprine model.
Weinzweig
Jeffrey
J
Burlington and Beverly, Mass.; Logan, Utah; and Providence, R.I. From the Department of Plastic Surgery, Lahey Clinic Medical Center; U.S. Department of Agriculture, Agricultural Research Service, Poisonous Plant Research Laboratory; Department of Plastic Surgery, Beverly Hospital; and Department of Plastic Surgery, Rhode Island Hospital, Brown University.
Panter
Kip E
KE
Patel
Jagruti
J
Smith
Darren M
DM
Spangenberger
Anthony
A
Freeman
M Brandon
MB
D000818:Animals; D002972:Cleft Palate / Q000196:embryology*; D004195:Disease Models, Animal; D006041:Goats / Q000196:embryology