Effect of cholesterol feeding on cholesterol biosynthesis in maternal and foetal rat liver

Hepatic cholesterol biosynthesis has been studied in rat foetuses whose mothers had been fed on a cholesterol rich diet during the last week of gestation. Foetal liver was found to be capable of synthesizing cholesterol from acetate in vitro. The rate of incorporation of labelled acetate into digitonin precipitable sterols, fatty acids and CO(2) in foetal liver was much higher than that found in maternal liver. Cholesterol feeding reduced the rate of sterol synthesis in maternal liver but it did not have any appreciable effect on foetal liver. In order to investigate whether this lack of feed-back control in foetal liver could be attributable to an obstacle to the placental transfer of dietary cholesterol. 14-C-cholesterol was administered to the pregnant rats and its distribution in maternal and foetal liver and plasma was studied. Our results indicate that placental transfer of cholesterol from mother to foetus occurs very slowly so that only a small proportion of labelled cholesterol is found in foetal plasma over a 48 hour period following the administration of radioactive cholesterol. Cholesterol transferred from the mother into the foetal plasma is efficiently taken up by the foetal liver. These findings would suggest that the low amount of dietary cholesterol transferred from the mother into the foetal plasma is not sufficient to activate the control mechanism of the cholesterol biosynthetic pathway in the foetal liver.