AIMIntrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio. METHODUsing HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence. RESULTSIn ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates >> unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2. CONCLUSIONUDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Intrahepatic cholestasis of pregnancy (ICP) is characterized by an increase in maternal serum concentrations of bile acids and sulphated progesterone metabolites. WHAT THIS STUDY ADDS• The accumulation of sulphated progesterone metabolites in the serum of ICP patients is associated with enhanced concentrations of progesterone. Although these compounds may be involved in the aetiopathogenesis of ICP, the magnitude of this accumulation does not correlate with the degree of hypercholanaemia in ICP patients.• The beneficial effect of ursodeoxycholic acid (UDCA) treatment includes a reduction of maternal hypercholanaemia, which is not dependent on the correction of progesterone metabolites accumulation.• In spite of marked increases in maternal serum concentrations of sulphated progesterone metabolites and bile acids in ICP patients, the concentrations of these compounds in foetal serum remain normal or are only moderately elevated, respectively. The latter can be corrected by treatment with UDCA.• The ABCG2 export pump located at the apical membrane of trophoblast cells plays an important role in the placental barrier for sulphated progesterone metabolites and bile acids. ABCG2 up-regulation during ICP, and further by UDCA treatment, ...

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