Mouse palatal width growth rates as an "at risk" factor in the development of cleft palate induced by hypervitaminosis A.

Abstract

Epidemiological studies revealed population differences in the frequency of cleft lip and palate, with wide faced, rapid growing populations having the highest incidence: Mongoloids > Caucasoids > Blacks. Laboratory studies have also demonstrated higher incidence of vitamin A-induced cleft palate in both rats and mice with rapid somatic growth rates compared to those with slower rates. The present study was designed to test the hypothesis that palatal width growth rates are significantly correlated with frequencies of cleft palate induced by hypervitaminosis A in seven strains of mice. Palatal width growth rates were calculated using 158 fetuses from 26 timed pregnant mice. Anterior and posterior palatal width growth rates during secondary palatogenesis were calculated between day 15 (n = 88) and day 18 (n = 70) gestational age. Anterior palatal width rates ranged from 0.106 mm/day (BALB/cByJ) to 0.219 mm/day (C57BL/6J), and rates for the posterior measure ranged from 0.111 mm/day (BALB/cByJ) to 0.179 mm/day (CBA/J). Vitamin A (10,000 IU/kg) was administered to an additional 26 timed pregnant mice on day 10 of gestation. The frequency of clefting, calculated from 181 fetuses at day 18 of gestation, was found to range from 52.4% +/- 9.7 (C3H/HeJ) to 96.3 +/- 6.4 (CBA/J). No significant correlation (P > 0.05) was found between palatal width growth rates and the frequencies of vitamin A induced cleft palate. It is concluded that if the rate of growth in the width of the palate is causative in clefting, it must be a pre-clefting (i.e., pre-shelf elevation) event and may only be detectable earlier than day 15 of gestation in the mouse.