Expression Of Placental Organic Anion Transporting Polypeptides OATP1A2,1B1,1B3 In Intrahepatic Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP), a specific complication in the second or. third trimester of pregnancy, is characterized by jaundice, pruritus, elevated serum aminotransferases and especially elevated bile acids. ICP poses little risk on the mother but the fetus has significantly increased risks of perinatal morbidity and mortality including preterm delivery, fetal distress and even sudden intrauterine death. As yet, the etiology and pathogenesis of ICP remain elusive and incompletely understood. It appears to be a multifactorial disease.The most characterize of ICP is the elevated bile acids in maternal serum; which may increase 10-20fold. Serum bile acid measurement is now considered to be the most suitable biochemical marker for both the diagnosis and monitoring of ICP. The risk of adverse fetal outcomes is thought to relate to maternal serum bile acid level, and several recent studies had shown that the expression of bile acid transporters was associated with the cholestatic diseases. In recent years, with the deepening of research in the pathogenesis of ICP and liver related transporters, whether there are some bile acids transporters in human's plancenta which plays a great role in substances exchange between the fetus and the mother caused researchers'attention. We hypothesized that the placental expression of bile acid transporters OATP1A2, OATP1B1 and OATP1B3 was altered in ICP and the current study was designed to investigate whether OATP1A2, OATP1B1 and OATP1B3 were differentially expressed in ICP placenta.Objectives:To investigate whether bile acids transporters OATP1A2, OATP1B1, OATP1B3 existed different expression between intrahepatic cholestasis of pregnancy (ICP) and normal placenta, to analysis the possibility of high fetal risk in ICP.Methods:30 ICP placentas, fetal and maternal serum were recruited and 30 normal pregnant placentas, fetal and maternal serum served as control. Gene expression of mRNA was analyzed by real-time PCR and Western blot was used to validate the protein expression. The localization of OATP1A2 and OATP1B3 were investigated by the immunohistochemistry.Results:Significantly elevated CG's level of fetal and maternal serum was associated with ICP, and the incidence of preterm labor and fetal distress was much high in ICP. OATP1A2 and OATP1B3 had significantly lower at the levels of mRNA and protein in ICP placenta compared with normal, protein of OATP1B1 was not found while mRNA had been observed variable expression for all the samples(Control VS ICP,7/30 VS 8/30). The localization of OATP1A2 and OATP1B3 were stained in the vasculo-syncytial membrane (VSM) and villlous syncytiotrophoblast (VSM＞＞syncytiotrophoblast).Conclusions:The data presented here suggests that down-regulation of transporters OATP1A2 and OATP1B3 may involve in the pathophysiology of ICP. Besides, the expression alteration of bile acids transporter genes, which cause the disorder of bile acids, may correlate with fetal risk. The localization of OATP1A2 and OATP1B3 at the vasculo-syncytial membrane (VSM) may be playing an important role in transporting bile acid between the fetus and the mother.