A Preliminary Study Of The Mechanism Of Fetal Anoxia In Intrahepatic Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is an important complication unique to pregnancy. In the viewpoint of maternity, it is benign except that pruritus is severe. In the fetus, however, the course is not the case. The disease is closely related to a high incidence of perinatal complications, including an increased fetal distress and preterm delivery, a higher incidence of meconium passage and an increased perinatal mortality rate. But the mechanism of fetal anoxia in intrahepatic cholestasis of pregnancy is not completely known.Many studies of the mechanism of fetal asphyxia in ICP have been performed in the aspects of placenta, bile acid and meconium resulting in umbilical vessels and placental chorionic veins constriction. These data all were from external cause of vessels constriction. Human non-innervated umbilical vessels are the only channel linking mother and fetus. It has been reported that different kinds of vasoactive substances can be secreted by human umbilical vein endothelial cells(HUVEC),which took part in controlling vessels tension by autocrine, paracrine and endocrine.To explore the pathogenesis of fetal anoxia in intrahepatic cholestasis of pregnancy, we investigated the structure, ultrastructure of HUVEC and placenta and performed the locating and quantitative studies of many kinds of vasoactive substances by primary cell culture of HUVEC, HE staining, electron microscopy, immunohistochemistry and radioimmunoassay.The main results are as follows:1. HUVEC in vitro of ICP had more constrictive vasoactive substances (nueropeptide Y ) and less relaxing vasoactive substances(substance P andsomatastatin) than those of normal pregnancy.2. The HUVEC in vivo and placenta of ICP expressed more constrictive vasoactive substances (nueropeptide Y) and less relaxing vasoactive substances(substance P and somatastatin) than those of normal pregnancy, which suggested an important substantial evidence to support the viewpoint that the umbilical cord spasm causes acute fetal anoxia.3. The abnormal structure of HUVEC of ICP was observed light- microscopically, and a large number of microfilaments were also observed electron microscopically in HUVEC and syncytiotrophoblasts of ICP, which offered a significant morphologic evidence to support the viewpoint that the umbilical cord spasm causes acute fetal anoxia. 4. The concentration of constrictive vasoactive substances (NPY, ET) of maternal serum, umbilical blood and HUVEC supernatant was lower in ICP than in normal pregnancy, which may be a dynamic reserve when vessel endothelial cells(VEC) suddenly release a large number of constrictive vasoactive substances under stress. These results show that the umbilical vessel is the channel to connect mother and fetus; besides, VEC, as a kind of inner cause of vessel constriction, has complicated functions which take part in fetal anoxia. Particularly, it would be more interesting to have further studies of the cytoskeletal system of HUVEC.