Bile acid conjugation in organ culture of human fetal liver.

An organ culture system for prolonged maintenance of human fetal liver has been developed and used to investigate the formation of bile acid conjugates. Multiple liver specimens were obtained from human abortuses and stillbirths ranging from 10 to 29 weeks of gestation. Within 3 hr of hysterotomy, small fragments of liver were established in organ culture. The morphological integrity of the explants was demonstrated by light and electron microscopy. Functional viability was determined by adding radiolabeled primary bile acid to the medium and assaying the taurine and glycine conjugates formed. Primary bile acid was taken up by the tissues, conjugated with taurine and glycine, and secreted into the medium at a constant rate during 10 days in vitro and in constant increments during a selected 24-hr period. The results establish that human fetal liver survives intact for periods up to 10 days in vitro. Taurine conjugates of the primary bile acids predominate throughout gestation and conjugates of cholic acid are synthesized in preference to those of chenodeoxycholic acid. Supplementation of the medium with taurine results in enhanced taurocholate formation with competitive inhibition of glycocholate synthesis, suggesting one acyl transferase system for both taurine and glycine. Finally, in medium supplemented with hydrocortisone there is a reversal of the glycine-taurine ratio seen in fetal liver.