[Epidermal growth factor regulates trophoblast proliferation and differentiation in an autocrine/paracrine manner]

Effects of epidermal growth factor (EGF) on the expression of trophoblast proliferation and differentiation were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from each trimester of gestation were cultured with or without EGF (100 ng/ml) in serum-free conditions. In order to determine the possible effect of EGF on the proliferation activity of villous trophoblasts, immunostaining with monoclonal antibody Ki-67 was used. On the other hand, the possible effect of EGF on the differentiated cellular function of villous trophoblasts was assessed by determining the ability to secrete hCG and hPL. In 4-5 week placenta, EGF and EGF receptor were found to be almost exclusively localized in cytotrophoblasts and EGF enhanced the proliferation of cytotrophoblasts without affecting the ability to secrete hCG and hPL, whereas in 6-12 week placenta, EGF and EGF receptor were predominantly localized in syncytiotrophoblasts and EGF stimulated the secretion of hCG and hPL without affecting the proliferation of cytotrophoblasts. These findings suggest that EGF has dual actions which independently affect trophoblast proliferation and differentiation in the first trimester of gestation in an autocrine manner. But, in the second and third trimesters of gestation, EGF mediates the expression of placental function in a paracrine manner.