The effect of vitamin A on fusion of mouse palates. I. Retinyl palmitate and retinoic acid in vivo.

C57B1 mice were given orally one, two , or three doses of ritinyl palmitate or retinoic acid on day 11, 12, 13, or 14 or pregnancy to determine 1) if it was possible to produce cleft palate at any time during palatal development of the mouse embryo, and 2) the maternal and fetal levels of vitamin A associated with the production of clefts. Whereas a single dose of either substance was sufficient to cause clefts on day 11 or day 12, three doses at 3-hour intervals were necessary to cause clefts on day 14. Most of these clefts were incomplete. Measurement of vitamin A levels in maternal serum and fetuses of dams after administration of retinyl palmitate or retinoic acid on day 11 and day 14 of pregnancy showed that transplacental passage of retinyl palmitate, retinol, and retinoic acid had taken place. Analysis of fetal serum on day 14 showed increase in levels of retinyl palmitate, retinol, and retinoic acid after dosing with retinyl palmitate, and in retinoic acid alone after dosing with retinoic acid. In both cases peak levels were observed within 3 hours. Our findings suggest that the effect of vitamin A on the developing mouse palate is direct, occurring soon after its administration, and that duration of exposure is as important as its concentration in vivo. The apparent change in sensitivity of mouse palate between day 11 and day 14 of pregnancy is discussed.