Functional Impairment Of Intrahepatic Cholestasis Of Preganacy To Fetal Liver

Intrahepatic cholestasis of pregnancy (ICP) is characterized by skin pruritus, raised maternal aminotransferases and bile acids, and less commonly, hyperbilirubinaemia in serum. Symptoms and laboratory abnormalities generally resolve within hours to days after delivery. ICP is associated with an increased risk of fetal distress, stillbirth and premature deliveries. The pathogenesis of ICP is not well known, especially that of fetal complications of ICP. It was generally accepted that when the bile salts deposited in placenta, the interspace of villus became narrow and the placental blood flow was decreased. The decrease of blood flow resulted in fetal anoxia, even death. Recently this theory was under challenge. It was reported that the transfer of oxygen across the placental membrane in ICP, detected by dual perfusion of the human placental lobule, was normal, and the placental blood flow detected by radioactivity isotope was not decreased in ICP. Moreover, the potential capacity of placenta-fetal circulation is so big that the narrow of villus interspace will not severe enough to make the fetal dead.The cytotoxicity of hydrophobic bile acids can lead to cell energy exhaustion and oxygen-derived free radidicals injury. Bilirubin is a kind of cytotoxic agents, which can inhibit the oxidative phosphorylation process and decrease the production of ATP. Under normal condition, bile acids and bilirubin from fetus are transported to maternal blood through placenta. InICP, the significantly increased bile acids and bilirubin in maternal serum impairs the function of placenta, so the discharging of fetal bile acids and bilirubin is not smooth. Moreover, the increased bile acids and bilirubin in maternal blood can enter fetal blood through placenta. Both can increase the bile acids and bilirubin in fetal blood. Whether or not the increased bile acids and bilirubin cause decrease of ATP production, decline the potential capacity of fetus and make it not endure the continuing status of hypoxia caused by vaginal delivery, resulting in fetal distress, stillbirth and fetal death. As best as we know there are not related reports now. In order to see whether the fetal hepatic function can be affected by bile acids, we detected changes of energy metabolism in livers of fetal rats born by mothers with ICP, studied the cytotoxicity of bile acids to cultured human fetal liver cells, explored the relationship between liver funtion despair and perinatal prognosis, and analysed the Bcl-2 expression in fetal livers of stillbirth in ICP.Energy metabolism and infrastructure changes of both maternal and fetal livers of ICPWe established animal models of ICP to detect energy metabolism changes of both maternal and fetal livers and to explore the mechanism of fetal distress. Nineteen 15-day-pregnant rats were randomly divided into 3 groups: Group E, Group EP and Group N. Rats in Group E were fed with ethinylestradiol (3.5mg/kg . d for 5days). Rats in Group EP were fed with ethinylestradiol (3.5mg/kg .d for 5days) and levonorgestrel (35mg/kg .d for 5days), while rats in Group N were fed with appropriate volume of propylene glycol. Total bile salt (TBA), aspartate aminotransferase (AST) and cholesterol (Ch) of the serum of the pregnant rats were measured with automatic biochemistry analysis meter. The amount of ATP of the fetal liverwas detected by reverse high pressure liquid chromatograph. The maternal and fetal livers were examined under light and electron microscopes. We found that AST, TBA and Ch were highest in Group EP, second highest in Group E. The ATP content in fetal livers was lowest in Group EP, second lowest in Group E. The differences among three groups were significant. Electron microscope observation found there were swelling and vacuolation in mitochondrions and dilation in cholangioles in both fetal and maternal hepatocytes in all the 3 groups. Among those, the changes in Group EP were most distinct, even there was demyelination in mitochondrions of fetal hepatocytes. The changes in Group E were...