Cholesterol synthesis and accretion within various tissues of the fetal and neonatal rat

The rate of cholesterol synthesis is reported to he higher in fetal relativ e to adult rats. Along with the observation that maternal diets high in fat and cholesterol are unable to alter the rate of cholesterol synthesis in t he fetus, this has been taken as indirect evidence that the fetal rat meets its cholesterol needs through de novo synthesis. This study quantified the rates of cholesterol synthesis and accumulation in the liver, brain, intes tine, and carcass of the fetal and neonatal rat and the placenta to determi ne whether these developing tissues are able to support their own cholester ol needs without the uptake of plasma lipoprotein cholesterol. The rate of cholesterol synthesis was determined in vivo using [H-3]water. The rate of cholesterol accumulation was determined by calculating the difference in ti ssue cholesterol content between 2 subsequent days of development. Total fe tal body cholesterol synthesis was sufficient to support the rate of choles terol accumulation. Fetal and neonatal liver synthesized cholesterol at a r ate in excess of cholesterol accumulation, suggesting hepatic secretion of cholesterol into the plasma. Before the onset of suckling, the rates of de novo cholesterol synthesis in the intestine, brain, and carcass were also s ufficient but not higher than the need for cholesterol accretion, After the establishment of suckling, the rate of cholesterol accumulation in the int estine and carcass was in excess of synthesis, suggesting that neonatal tis sues derive some of their cholesterol from dietary milk or liver. These stu dies suggest that the perinatal rat does not require exogenous cholesterol to support tissue cholesterol accretion. However, the fetal liver may suppo rt cholesterol accretion in other tissues through rates of synthesis in exc ess of accumulation and secretion into plasma. The placenta may derive some cholesterol from the maternal and/or fetal plasma. Copyright (C) 2001 by W .B. Saunders Company.