Effect of maternal cholestasis on bile acid transfer across the rat placenta-maternal liver tandem

Cholestasis of pregnancy induces alterations in bile acid transport by huma n trophoblast plasma membrane (TPM) vesicles. We investigated whether mater nal cholestasis affects the overall ability of the rat placenta to carry ou t vectorial bile acid transfer from the fetus to the mother. Complete obstr uctive cholestasis (OCP) was maintained during the last week of pregnancy a nd released at term (day 21), before experiments were performed. In situ si ngle-pass perfusion of one placenta per rat with 250 nmol [C-14]glycocholic acid (GC) revealed an impaired uptake in OCP rats (2.28 vs. 5.53 nmol in c ontrol rats). Approximately 100% of GC taken up by control placentas was se creted in maternal bile over 120 minutes (5.38 nmol), whereas this was only 61% (1.40 nmol) of the GC taken up by OCP placentas. When 5 nmol GC was ad ministered through the jugular vein no significant difference between both groups in total GC bile output was found. The efficiency (V-max/K-M) of ade nosine triphosphate (ATP)-dependent GC transport by vesicles from the mater nal side of TPM was decreased (-41%) in OCP. Moreover, histological examina tion of the placentas suggested a reduction in the amount of functional tro phoblast in the OCP group. This was consistent with a lower antipyrine diff usion across the placenta in these animals. In sum, our results indicate th at maternal cholestasis affects the ability of the placenta to efficiently carry out bile acid transfer from fetal to maternal blood. Changes in both the structure and the functionality of the chorionic tissue may account for this impairment.