Detecting On Mechanism Placenta Dysfunction Of Intrahepatic Cholestasis Of Pregnancy

Objective: This study was undertaken to investigate the reasons on placenta dysfunction of intrahepatic cholestasis of pregnancy (ICP). This kind of dysfunction may be caused by the changes of placenta ultrastructure, cell apoptosis in placenta, and over expression of control gene on placenta with ICP. The causes of higher rate on fetal death, stillborn and neonatal death with ICP was explored and the theoretic basis for treatment in ICP was provided. Methods: Pregnant women with ICP and normal pregnancy were recruited from Cesarean section before the onset of labor in our hospital from Jan, 1999 to Dec, 2001. (1) ICP group with 28.42 years old (26-36) for 37+5(36~41) weeks. (2) Control group with 28.29 years old (24 — 33) for 39+1(37~41) weeks. Thediagnosis of ICP was defined according to Chinese Obstetric and Gynecology, including: l)Parts or whole debilitating pruritus in the second or the third trimester. 2) With markedly elevated serum bile acids and mild or medium elevated serum transaminase level. 3)Pregnancy was only reason that caused the disease of skin and abnormal biochemistry results. 4)The negative results of HBV and HCV were taken. 5)Symptom and laboratory abnormalities generally resolved within hours or days after delivery. The TUNEL (TdT- mediated dUTP nick end labeling) and immunol-hisochemistry methods were used for 31 placental sample with ICP and 31 normal placental sample to detect apoptosis index and the expression of Fas, FasL, P53, bax and bcl-2 in placenta tissues. Ultrastructure of placenta was observed from 10 cases of ICP pregnant women and one normal pregnant woman. Result: Compared with normal placenta, the placenta ultrastructure in ICP had significantly changes, including: the decrease or disappear of microvilli on the surface of placenta, the dilation of rough endoplasmic reticulum and smooth endoplasmic reticulum significantly, solid contract of syncytotrophoblast, the hyperplasia and dilation of microvascular in villus clearance. The results of the degree of apoptosis on the placenta and the regulation of control genes of apoptosis were found : The apoptosis index in placental syncytotrophoblast, decidual cells and mediate cell in ICP group was significantly higher than that in control group ( p < 0.05 = . The expression of P53, Bax, Fas in placenta syncytotrophoblast cell in ICP group was higher than those of control (p<0.05= and the expression bcl-2, FasL of this position in ICP was lower than control group (p<0.05 = in placenta syncytotrophoblast cell. The expression of P53, Bax, in decidual cell in ICP group was higher(p<0.05). The expression of bcl-2 on these positions in ICP group was lower than that in control group (p <0.05) . The expression of Fas in placental decidual cell in ICP group was not significantly higher(p> 0.05). The expression of Bcl-2,FasL ofthese positions in ICP group was lower than that in control group (p< 0.05) . The expression of P53 , Bax, in mediate cell in ICP group was higher(p<0.05).The expression of bcl-2 on these positions in ICP group was lower than that in control group (p<0.05) . The expression of Fas in placental mediate cell in ICP group was not significantly higher (p> 0.05) . The expression of FasL of these positions in ICP group was lower than that in control group (p<0.05) . Conclusions: Compared with normal placenta, the placenta ultrastructure had significantly changes. The changes destroyed the integrity function of placenta. Apoptosis in placental syncytotrophoblast, decidual cells and mediate cell in ICP group was significantly higher, which may be related to the placental dysfunction. Abnormal over expression of P53, bax and the lower expression of bcl-2 on placental tissue of ICP was the main reason of placental apoptosis. Abnormal expression of Fas and FasL on placental tissue may destroy the immunotolerance between the mother and the fetus and increase placental apoptosis that may be related to the placental dysfunction.