Owing to the immaturity of the hepatobiliary system the placenta-maternal liver tandem must carry out the elimination of fetal bilirubin and bile acids that are produced during intrauterine life. This excretory route is impaired by maternal hypercholanaemia. The aim of the present study was to characterize this alteration and to investigate the effect of ursodeoxycholic acid treatment (UDCA; intragastric, 60 µg (100 b.w.)^-1 day^-1) in pregnant rats, in which hypercholanaemia was induced by obstructive cholestasis for the last week of pregnancy (OCP) under anaesthesia. Obstruction was released on day 21 and bile was drained to reach steady state in bile acid output before carrying out the experiments under pentobarbital anaesthesia (approved by the Ethical Committee of the University of Salamanca).

Real-time quantitative RT-PCR indicated that the level of placental lactogen II mRNA, a trophoblastic marker, was reduced in OCP but normalized in OCP+UDCA.

The trophoblastic expression of organic anion transporter polypeptides (Oatp1, Oatp2 and Oatp4) and multidrug resistance associated proteins (Mrp1, Mrp2 and Mrp3) was enhanced at similar levels in both OCP and OCP+UDCA although, in general, the overall expression in the whole placenta was OCP+UDCA > OCP ▓ge│ control. However, kinetic analysis of ATP-dependent [¹⁴C] glycocholate transport by apical membrane vesicles isolated from rat trophoblast revealed that transport efficiency (V_max/K_m) was control ▓Dgr│{special} OCP+UDCA > OCP. Electron microscopy studies revealed that OCP induced loss of trophoblastic tissue together with morphological alterations that included the disappearance of plasma membrane microvilli. The functional tissue able to carry out transplacental exchange was evaluated by the diffusion of antipyrin that was reduced in OCP and partially restored by UDCA. The ability to secrete [¹⁴C] glycocholate into bile after infusion into the umbilical artery of one ‘in situ‘ perfused placenta or through the maternal jugular vein was dramatically reduced in OCP due to impairments in both placental transfer and liver secretion. Our results indicate that maternal hypercholanaemia induced morphological and functional changes that were in part prevented by UDCA, which had beneficial effects on both components of the placenta-maternal liver tandem excretory pathway. At the placental level where the effects were stronger, these include preservation of the amount and structure of the trophoblast and enhanced expression and function of carrier proteins involved in placental transfer of bile acids and other cholephilic organic anions. This may account for the fact that maternal and fetal body weight, together with the number of fetuses per pregnancy, were reduced by OCP and restored by UDCA treatment.