Biliary Bile Acid Composition of the Human Fetus in Early Gestation

Abstract

Using analytical techniques, which included capillary column gas-liquid chromatography and mass spectrometry, detailed bile acid profiles were obtained for 24 fetal bile samples collected after legal abortions were performed between the 14th and 20th wk of gestation. Qualitatively, the bile acid profiles of all fetal bile samples were similar. The predominant bile acids identified were chenodeoxycholic and cholic acid. The presence of small but variable amounts of deoxycholic acid and traces of lithocholic acid suggested placental transfer of these bile acids from the maternal circulation. 3β-Hydroxy-5-cholenoic acid was detected at higher levels than lithocholic acid. A conspicuous feature of the profiles was the presence of bile acids with hydroxyl groups at positions C-1 and C-6, and one other nuclear position of unknown origin, indicating fetal hepatic synthesis via pathways different from those normally seen in the adult. Quantitatively total biliary bile acid concentrations were extremely low (<0.05 mM) before wk 17 of gestation, but thereafter concentrations markedly increased reflecting a possible surge in bile acid synthesis; however, the ratio of cholic:chenodeoxycholic acids remained relatively constant over this period (mean ± SD = 0.85 ± 0.36) and different from that reported for the healthy newborn (ca. 2.5) and adult (ca. 1.6). These data indicate an immaturity in hepatic 12α-hydroxylation of bile acids during early development and may explain why other pathways, in particular 1β and 6α-hydroxylation, are activated at this stage of life.