retinol-acetate and Cleft-Palate

The influence of ethanol consumption on cleft palate induction by methylmercury, cortisone, and retinyl acetate was investigated in Swiss white mice. Consumption of 20% ethanol throughout gestation significantly increased the incidence of cleft palate compared to water-fed mice, when methylmercury was given on four consecutive days (days 9-12, 5 mg/kg of body weight). Ethanol also increased the incidence of cleft palate in mice given retinyl acetate (3,400 or 5,100 IU) on day 12, compared to retinol acetate-treated mice given water, but did not affect cleft palate induction by cortisone (2.5 mg/d, days 8-11). Ethanol significantly reduced fetal weight in the presence or absence of the three teratogens, but the results do not support a hypothesis that growth retardation is directly responsible for the potentiating action of ethanol. It may be that ethanol acts to increase cleft palate induction by some teratogens by retarding fetal developmental processes.

Topics: Alcohol Drinking; Animals; Cleft Palate; Cortisone; Diterpenes; Drug Synergism; Eating; Ethanol; Female; Gestational Age; Methylmercury Compounds; Mice; Pregnancy; Retinyl Esters; Vitamin A

Both retinoic acid and retinyl acetate, administered in high doses on days 13--15 of gestation, are capable of causing a 90 per cent incidence of cleft palate in Charles River rats. However, an attempt to develop as in vivo rabbit model system for the induction of clefts via hypervitaminosis A was unsuccessful. In the rat, the retinoic acid form of vitamin A is the more potent teratogen, inducing clefts at less than half the dose required to produce them with retinyl acetate. Histologic examination of fetal rat heads confirmed the biochemical evidence that retinoic acid is the more potent teratogen. Both forms of vitamin A prevented palatal shelf reorientation from occurring at the correct gestational age. The retinyl acetate treatment delayed the rotation for approximately 12 hours, the retinoic acid for at least 48 hours.

Topics: Animals; Cleft Palate; Disease Models, Animal; Diterpenes; Palate; Rabbits; Rats; Retinaldehyde; Retinyl Esters; Teratogens; Tretinoin; Vitamin A