Relationship between bile acid transplacental gradients and transport across the fetal-facing plasma membrane of the human trophoblast.
Bile acids and bilirubin are synthesized by the fetal liver very early on during intrauterine life. The main fate of these compounds is to be transferred to the mother. This excretory role of the placenta is primarily determined by the ability of the trophoblast to transport them, which is believed to occur mainly by carrier-mediated processes. The aim of this study was to investigate the role of the cholephilic organic anion exchanger located in the fetal-facing plasma membrane of the human trophoblast in placental "biliary-like" function. No relationship between the magnitude of transplacental gradients for total bile acids and bilirubin was found. However, transport studies, which were carried out by using purified plasma membrane vesicles derived from the fetal-facing pole of the human trophoblast, revealed that [14C]taurocholate transport was affected by both another bile acid (taurochenodeoxycholic acid) and a non-bile acid cholephilic organic anion (bromosulfophthalein). On plotting the ability of different major bile acid species to inhibit radiolabeled taurocholate uptake by these vesicles versus their concentrations in fetal serum or the magnitude of their transplacental gradients, inverse relationships were found. Lower fetal serum concentrations and transplacental gradients were found for bile acid species with higher abilities to affect this transport and presumably to interact with the carrier. By contrast, the magnitude of the transplacental gradient for bile acid species was not correlated with their hydrophobic/hydrophilic balance, as would be expected if diffusion across the lipidic structures of the placental barrier would be the major pathway for the flux of bile acid across this organ.(ABSTRACT TRUNCATED AT 250 WORDS)
D001647:Bile Acids and Salts / Q000378:metabolism* / Q000493:pharmacokinetics; D001663:Bilirubin / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D005321:Extraembryonic Membranes / Q000502:physiology*; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012016:Reference Values; D014327:Trophoblasts / Q000378:metabolism*
D001647:Bile Acids and Salts; D001663:Bilirubin