Preliminary Study Of Bile Acid Secretion Of Placenta Mediated By Abcb4 Gene

Background Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease normally occurring in the second and third trimester of pregnancy. Although ICP is not significantly harmful to maternal health, it increases the risk of fetal distress, preterm delivery, meconium staining during delivery, intrauterine death and stillbirth. The aetiology and pathogenesis of ICP is still unknown. Clinical and epidemiologic studies to present demonstrated that genetic and hormonal factors were mainly involved in the mechanism. The prevalence of ICP has obvious familial, racial and regional characteristics. With the development of medical molecular biology, people have found and identified ICP related genes:ABCB4,ABCB1 and ATP8B1. They encode carrier proteins in hepatocellular membrane which are involved in bile secretion. Mutations of ICP related genes could cause genetic ICP, however, the expression of these three genes in human placenta is not well understood. Whether they are involved in bile acid secretion of placenta and related to perinatal unfavourable prognosis of ICP needs to be studied.Objective To investigate the relationship between bile acid level and perinatal unfavourable prognosis of ICP by detection of maternal serum levels of bile acid, transaminase and bilirubin. To approach the relationship between ABCB4 gene and bile acid secretion of placenta by detection of ABCB4 and its products in placenta.Meterials and Methods Collect 30 pregnant women with and without ICP, respectively. Detect the bile acid levels of maternal and umbilical blood by radioimmunoassay. Assess the maternal serum of bilirubin and transaminase using chemical oxidation and enzyme kinetics. Evaluate the relative expression of mRNA of ABCB4 in placenta of both groups through reverse transcription polymerase chain reaction (RT-PCR). Locate the product of ABCB4 in placenta and detect its expression in placenta of both groups by immunohistochemisty. Results were subjected to statistical analysis using SPSS 12.0 software with the significance level set at P < 0.05. Results Results (1) The average maternal serum bile acid level and Alanine Transaminase of ICP were higher than those of the controls (P<0.001). (2) Both umbilical arterial blood and maternal bile acid level in ICP were higher than those in controls (P<0.001). And the bile acid level of maternal serum blood was in positive correlation with that of umbilical blood in ICP (r=0.588), however there were correlation between them in controls. (3) ABCB4 mRNA could be detected in both placentas, and the expression level of ABCB4 mRNA in ICP was significantly lower than that in controls (P<0.001). The level of ABCB4 mRNA was in negative correlation with the level of bile acid in maternal serum and umbilical arterial blood. (4) MDR3P-gp, the product of ABCB4, could be detected in syneytiotrophoblast of both placentas, however, the level in ICP was obviously lower than in controls.Conclusions (1) It demonstrated that dysfunction of bile acid secretion of placenta might contribute to perinatal unfavourable prognosis of ICP; (2) It indicated that ABCB4 gene and its product were involved in bile acid secretion of placenta.