Abstract
BackgroundUrsodeoxycholic acid (UDCA) administration in intrahepatic cholestasis of pregnancy (ICP) induces bile acids (BA) efflux from the foetal compartment, but the molecular basis of this transplacental transport is only partially defined.AimTo determine if placental breast cancer resistance protein (BCRP), able to transport BA, is regulated by UDCA in ICP.Methods32 pregnant women with ICP (14 untreated, 34.9±5.17 years; 18 treated with UDCA - 25 mg/Kg/day, 32.7±4.62 years,) and 12 healthy controls (33.4±3.32 years) agreed to participate in the study. Placentas were obtained at delivery and processed for membrane extraction. BCRP protein expression was evaluated by immunoblotting techniques and chemiluminescence quantified with a luminograph measuring emitted photons; mRNA expression with real time PCR. Statistical differences between groups were evaluated by ANOVA with Dunn’s Multiple Comparison test.ResultsBCRP was expressed only on the apical membrane of the syncytiotrophoblast. A significant difference was observed among the three groups both for mRNA (ANOVA, p = 0.0074) and protein (ANOVA, p<0.0001) expression. BCRP expression was similar in controls and in the untreated ICP group. UDCA induced a significant increase in placental BCRP mRNA and protein expression compared to controls (350.7±106.3 vs 100±18.68% of controls, p<0.05 and 397.8±56.02 vs 100±11.44% of controls, p<0.001, respectively) and untreated ICP (90.29±17.59% of controls, p<0.05 and 155.0±13.87%, p<0.01).ConclusionOur results confirm that BCRP is expressed only on the apical membrane of the syncytiotrophoblast and show that ICP treatment with high dose UDCA significantly upregulates placental BCRP expression favouring BA efflux from the foetal compartment.
Highlights
Intrahepatic cholestasis of pregnancy (ICP), a liver disorder unique to pregnancy, predominantly occurs during the third trimester of gestation
Our results confirm that breast cancer resistance protein (BCRP) is expressed only on the apical membrane of the syncytiotrophoblast and show that intrahepatic cholestasis of pregnancy (ICP) treatment with high dose Ursodeoxycholic acid (UDCA) significantly upregulates placental BCRP expression favouring bile acids (BA) efflux from the foetal compartment
While no certain cause has been identified, impaired bile acids (BA) metabolism leads to increased BA accumulation in the foetal compartment [4]
Summary
Intrahepatic cholestasis of pregnancy (ICP), a liver disorder unique to pregnancy, predominantly occurs during the third trimester of gestation. ICP is characterized by pruritus and biochemical alterations in liver tests which fully resolve after delivery [1,2], and is associated with an increased risk of foetal distress, preterm delivery and sudden intrauterine foetal death [3]. Given the substantial foetal risk, ICP is widely considered a serious clinical problem [3]. While no certain cause has been identified, impaired bile acids (BA) metabolism leads to increased BA accumulation in the foetal compartment [4]. Ursodeoxycholic acid (UDCA) administration in intrahepatic cholestasis of pregnancy (ICP) induces bile acids (BA) efflux from the foetal compartment, but the molecular basis of this transplacental transport is only partially defined
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