Maternal-fetal Bile Acid Profiles And Placental Expression Of OATP-A, OATP-C In Intrahepatic Cholestasis Of Pregnancy

Objectives To investigate the plancetal expression of OATP-A andOATP-C during pregnancy. To explore the change of plancetal expression ofOATP-A in gravidas complicated with intrahepatic cholestasis of pregnancy(ICP), as well as their relationship with total bile acids (TBA) and 9 kinds ofbile acids (CA, DCA, CDCA, TCA, TDCA, TCDCA, GCA, GCDCA andLCA) levels in maternal and umbilical cord serum. To evaluate the roles ofOATP-A and OATP-C in the pathological mechanism of ICP.Methods Maternal,umbilical venous blood and placentas were collectedfrom 20 ICP (ICP group) and 20 normal 3rd trimester pregnancy (controlgroup), as well as placentas from 8 1st trimester and 7 2nd trimester normalpregnancy. TBA and 9 kinds of bile acids levels were measured byvelocimetry and HPLC- MS/MS respectively. Real time RT-PCR was appliedfor the measurement of placental OATP-A, OATP-C mRNA expression. Thelocalization of OATP-A was analyzed by immunohistochemistry.Results (1) Both maternal and umbilical cord serum TBA levels in ICPgroup were significantly higher than those in control group(46.15±62.82 VS 2.82±1.82μmol/L; 18.23±16.77 VS 4.79±1.26μmol/L, P＜0.05). Maternalserum TBA level was significantly higher than that in umbilical serum of ICPgroup (46.15±62.82 VS 18.23±16.77μmol/L, P＜0.05).In the control group,umbilical serum TBA level was higher than that in the maternal blood(2.82±1.82 VS 4.79±1.26μmol/L, P＜0.05). (2) Maternal serum levels ofCA,TCA,TDCA,TCDCA,GCA,GCDCA and umbilical serum levels ofCA,TCA,TDCA,GCA,GCDCA,LCA were higher in ICP group than thosein control group (P＜0.05), While maternal serum DCA level was lower inICP group than that in control group (P＜0.05). In ICP group, DCA,TCA,TDCA,TCDCA,GCA levels were higher in maternal serum than those inumbilical serum(P＜0.05). In normal group, DCA,TDCA,LCA levels werehigher, while TCDCA level was lower in maternal serum than those inumbilical serum(P＜0.05). (3) OATP-A mRNA was detected in normal 1st,2nd, 3rd trimester and ICP placentas, transcript of OATP-C was not detectedin these placentas. Placental OATP-A mRNA expression was higher in ICPgroup than that in control group (40.72±31.46 VS 21.54±15.65, P＜0.05).No significant difference was found in placental OATP-A mRNA expressionamong normal 1st, 2nd and 3rd trimester placentas. (4) OATP-A expressionwas detecterd in trophoblast by immunohistochemistry. (5) In ICP group, anegative correlation was found between the placental OATP-A mRNAexpression and the umbilical serum TCDCA concentration (r=-0.579,P＜0.05). In control group, negative correlations were found between theplacental OATP-A mRNA expression and the maternal serum TCDCA,GCA,GCDCA concentrations (r=-0.448, -0.477, -0.499 respectively,P＜0.05). Conclusion (1) Our results suggested that both maternal and fetal serumbile acids levels, especially the conjugated primary bile acids are increased inICP than those in normal pregnancies. (2) OATP-A mRNA expression is upregulated in ICP placenta, which may represent a compensatory(anti-cholestatic) mechanism for increased bile acids levels in ICP.