Expression Of Epidermal Growth Factor Receptor In Human Trophoblast Cells

Placenta occupies a unique position as the site of production of both protein and steroid hormones and plays a central role in the endocrinology of pregnancy. The trophoblast which displays highly proliferative properties between normal and tumor cells plays an important role in the establishment and maintenance of pregnancy. Many regulatory factors involved in the process of proliferation and differentiation of trophoblast were examined. Epidermal Growth Factor (EGF) plays an important role in normal cellular growth and differentiation and acts on its placental target cells, i.e. the trophoblasts,via a specific receptor (EGFR) which belongs to the tyrosine kinase receptor family. Human trophoblast cells express both EGF and EGFR, and that EGF plays a major role in placental implantation,growth and differentiation.An Alteration of EGFR biological activity directly interferes with the differentiated function and proliferation of trophoblast and the fetoplacental development. Objectives1. To study the expression of EGFR and EGFRmRNA in human trophoblast cells of different pregnancy phases.2. To investigate the pathological changes in ultrastructure of placental tissues in patients with pregnancy induced hypertension (PIH) and to clarify the expression of EGFR and EGFRmRNA in placenta so as to discuss the pathogenesis of PIH.3. To study the expression of EGFR and EGFRmRNA in JAR choriocarcinoma cells and to explore the effect of EGFR on the pathogenesis of choriocarcinoma.Methods1. The EGFR expression in human trophoblast cells of dififferent pregnancy phases were shown by immunohistochemical method (ABC) and Western blot,and the related quantity of EGFRmRNA was analyzed by RT-PCR method.2. The ultrastructure of the placental tissue was observed under electron microscope. The immunohistochemical method and Western blot were preformed to show the expression of EGFR and RT-PCR method was applied to determine the expression of EGFR mRNA in placenta trophoblast of pregnancy with PIH.3. EGFR of JAR was determined by immunohistochemical method and EGFRmRNA was analyzed by RT-PCR method.Results1. EGFR protein located on cell membrane,nuclear membrane and in the cytoplasm, characterized in both syncytiotrophoblast and cytotrophoblast. Expressiong of EGFR in placenta in the first trimester was significantly stronger than that in placenta of the second and third trimesters(P<0.01).The related quantity of EGFRmRNA expression in the placenta in the first trimester was significantly stronger than that in placenta of the second and third trimesters(P<0.01).2. Tha pathological changes in ultrastructure of placental tissues in study group were quite obvious.Compared with that of normal pregnancy,the expression of EGFR as well as EGFRmRNA in placenta from pregnancies complicated with PIH decreased significantly(P<0.01).3. EGFR mRNA and protein levels in JAR were significantly higherthan those in normal trophoblast(p<0.01). Conclutions1. Expression of EGFR and EGFRmRNA were different throughout the gestational period, which related to HCG concentration of normal human pregnancy.2. The obvious pathological changes were found in ultrastructure of placental trophoblast of study group. Decreased protein expression of placental EGFR, influenced by the decrease of EGFR gene transcript, was found in women with PIH ,and that may play a role in the pathogenesis of PIH.3. EGFR overexpression may contribute to the uncontrolled proliferation of choriocarcinoma cells in general.