The influence of ursodeoxycholic acid and maternal cholestasis on bile acid transport across the placenta

摘要

During intrauterine life, when tissues of the enterohcpatic circuit are not yet mature and the fetal liver is already able to synthesize bile acids (BAs) but not to secrete them into bile, efficient transfer of fetal BAs across the placenta, together with normal maternal hepatobiliary function, are crucial for BA levels in fetal serum to be maintained within the physiological range. The trophoblast plays a key role in this transfer. In addition to a small diffusional component for non-ionic forms of BAs, carrier-mediated transport systems are responsible for the translocation of BAs across this epithelium (Figure l). Uptake across the basal membrane is mediated by anion : BA exchanger(s)4'5, which display(s) reversible properties6 and probably belong to the family of organic anion-transporting polypeptides (OATPs or the SLC21 family). Indeed, in a combination of RT-PCR and sequencing, we have previously detected in the rat placenta the presence of isoforms Oatpl, Oatp2 and Oatp4 (data not shown) that are able to transport BAs7.