Bile acid metabolism in fetal sheep; perinatal changes in the bile acid pool

1. A chronic fetal bile fistula model was developed in sheep which allowed observations on fetal bile for periods of up to 10 days. A comparison of fetal, lamb and adult bile acids was made in bile fistula animals. 2. Bile was analysed by thin layer chromatography, gas liquid chromatography, and high pressure liquid chromatography. Fetal bile contained a much greater proportion of chenodeoxycholic acid (42.0 +/- 1. S.E. of mean 3.0% of total bile acids by high pressure liquid chromatography) than lamb bile (8.1 +/- 1.9%) or adult bile (5.4 +/- 0.6%). The corresponding figures for cholic acid were fetal: 45.8 +/- 2.9%, lamb: 89.1 +/- 2.9%, and adult: 75.2 +/- 2.6%. Deoxycholic acid, a secondary bile acid, was present in fetal bile (12.2 +/- 4.9%). In the lamb, deoxycholic acid comprised only 2.8 +/- 1.1% of total bile acids, compared with 19.3 +/- 2.9% in adult sheep. Taurine conjugates predominated in sheep bile, but this predominance was least marked in lamb bile. 3. The fetal bile acid pool (101 +/- 13 mu mole/kg) was significantly smaller than the neonatal pool (214 +/- 26 mu mole/kg, P < 0.01). This increase in pool size, together with the increased proportion of cholic acid, suggests a rapid rise in cholic acid synthesis soon after birth. 4. Bile acid synthetic rates were estimated from bile acid secretion rates at the nadir of the washout curves. The values obtained were 0.71 +/- 0.18 mu mole/kg.hour (adult), 0.47 +/- 0.16 mu mole/kg.hour (lamb), and 0.35 +/- 0.08 mu mole.hour (fetus). 5. In the fetus and in pregnant adult sheep, the normal increase in bile acid synthesis in response to depletion of the bile acid pool was much less marked. 6. In the fetus, biliary secretion of cholesterol and phospholipid ran parallel with bile acid secretion. Bile lipid composition was similar to that in the adult. 7. Fetal bile water production was higher, relative to bile acid secretion, than lamb or adult bile water secretion.