Vascular endothelial growth factor but not placental growth factor promotes trophoblast syncytialization in vitro

OBJECTIVE: The object of this study tvas to determine the effect of epithelial growth factor (EGF), vascular endothelial growth factor (VEGF), and placental growth factor (PIGF) on the differentiation of first-trimester and term cytotrophoblasts. METHODS: The first-trimester trophoblasts were isolated from villous tissue obtained at suction termination (n = 5), and the term trophoblasts were isolated from placentas (n = 6) at elective cesarean. Cultured cells were stimulated with EGF, V-EGF, or PIGF at 0.5, 5, and 50 ng/mL, in the presence or absence of N-G-nitro-L-arginine methyl ester hydrochloride (10(-4) M). Syncytialized trophoblasts were identified by immunostaining with antidesmosomal protein and anti-cytokeratin-7, whereas nuclei were counted in each syncytia using hematoxylin. RESULTS: Without treatment, background levels of syncytialization were significantly ln her in term preparations than first-trimester cells. With VEGF and EGF, the number and size of syncytia increased significantly for the first-trimester cytotrophoblasts (P < .05). Neither VEGF nor EGF had any effect oil the syncytialization of cultured cells at term. Nitric oxide showed no involvement in syncytial induction, and PIGF had no effect on syncytialization of cytotrophoblasts, from either the first or third trimester. CONCLUSION: Both EGF and VEGF appeared to enhance the in vitro syncytialization of first trimester cytotrophoblasts. (J Soc Gynecol Investig 2001; 8:341-6) Copyright (C) 2001 by the Society for Gynecologic Investigation.