RELATIONSHIP BETWEEN BILE-ACID TRANSPLACENTAL GRADIENTS AND TRANSPORTACROSS 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 b e transferred to the mother. This excretory role of the placenta is pr imarily 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 orga nic anion exchanger located in the fetal-facing plasma membrane of the human trophoblast in placental ''biliary-like'' function. No relation ship 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 th e fetal-facing pole of the human trophoblast, revealed that [C-14]taur ocholate transport was affected by both another bile acid (taurochenod eoxycholic acid) and a non-bile acid cholephilic organic anion (bromos ulfophthalein). On plotting the ability of different major bile acid s pecies to inhibit radiolabeled taurocholate uptake by these vesicles v ersus their concentrations in fetal serum or the magnitude of their tr ansplacental 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 presum ably to interact with the carrier. By contrast, the magnitude of the t ransplacental gradient for bile acid species was not correlated with t heir hydrophobic/hydrophilic balance, as would be expected if diffusio n across the lipidic structures of the placental barrier would be the major pathway for the flux of bile acid across this organ. In summary, these results indicate that carriers located in the basal plasma memb rane may play an important role in the control of the qualitative and quantitative fetal-maternal bile acid exchange. Moreover, they suggest that although both bile acids and bilirubin may share this pathway fo r access to the trophoblast, other additional mechanisms are probably responsible in part for the control of the magnitude of their transpla cental gradients.