Effect of chenodeoxycholic acid feeding during gestation in the rat on bile acid metabolism and liver morphology.

Chenodeoxycholic acid (CDCA) was fed to pregnant rats at the 0.25% level in the diet from Day 11 of gestation to delivery in order to evaluate the effects on (1) maternal tissue bile acid composition, (2) neonatal tissue bile acid composition and cholesterol-7 alpha-hydroxylase activity, and (3) maternal, neonatal, and postnatal liver morphology. Feeding CDCA increased maternal lithocholic acid while significantly decreasing deoxycholic acid, cholic acid, and total bile acids. Feeding CDCA resulted in a significantly higher chenodeoxycholic acid pool in the neonates while neonatal plasma cholesterol and the 7 alpha-hydroxylation of cholesterol was not significantly affected. Morphological examination of maternal, neonatal, and postnatal rat liver revealed no significant hepatotoxicity. This investigation has shown that (a) neonates of CDCA fed dams have a significantly greater pool of CDCA, suggesting maternal-to-fetal transfer of dihydroxy bile acids, (b) neonatal cholesterol-7 alpha-hydroxylase activity and total tissue bile acid pools are not significantly altered by increased pool of CDCA, and (c) no hepatotoxic effects on maternal, neonatal, and postnatal livers were evident with gestational feeding of CDCA at the 0.25% level in the rat.