Human chorionic gonadotropin and its free β-subunit stimulate trophoblast invasion independent of LH/hCG receptor

Both paracrine and autocrine factors are involved in the regulation of trophoblast invasion. One of these factors is human chorionic gonadotropin (hCG), which stimulates trophoblast invasion. The stimulatory activity has especially been ascribed to a hyperglycosylated form of hCG (hCG-h) that is expressed in early pregnancy. We compared the stimulatory activities of different forms of hCG and its free beta-subunit (hCG beta) on trophoblast invasion. hCG, hCG-h, hCG beta, and its hyperglycosylated form (hCG beta-h) stimulated the invasion of JEG-3 choriocarcinoma cells. The stimulatory effect of hCG beta was also confirmed with primary human trophoblasts. Down-regulation of the LH/hCG receptor by RNA-interference did not significantly reduce the effect of hCG beta and hCG on cell invasion. Increased invasion was associated with increased levels of MMP-2, MMP-9 and activity of uPA. Our findings suggest that hCG, hCG beta and their hyperglycosylated forms stimulate the invasion of trophoblast cells independent of the classical LH/hCG-receptor. (C) 2013 Elsevier Ireland Ltd. All rights reserved.