Hyperglycosylated hCG Is a Marker of Early Human Trophoblast Invasion

Context: Human chorionic gonadotropin (hCG) is the major pregnancy glycoprotein hormone whose maternal concentration and glycan structure change all along pregnancy. hCG is mainly secreted by the syncytiotrophoblast covering the chorionic villi, but little is known about the source of hyperglycosylated hCG (hCG-H) production. Objective: The objective of the study was to analyze expression and secretion of hCG and hCG-H in vitro during human trophoblastic cell differentiation, in situ in first-trimester placentas, and in maternal sera during early pregnancy. Design: hCG and hCG-H were measured in cell supernatants from primary cultures of first-trimester placenta trophoblastic cells, which differentiate in vitro into syncytiotrophoblast or invasive extravillous cytotrophoblasts (evct). hCG-H immunodetection were performed on 9 wk gestation (WG) placental tissue sections. Total hCG and hCG-H were quantified by chemiluminometric assay in 539 maternal sera collected between 9 and 19 WG during normal pregnancies. Results: In vitro, hCG secretion reached 37 ng/ml per mu g DNA during syncytiotrophoblast formation but contained few hCG-H (2-5% of total hCG). In contrast, hCG secretion (20 ng/ml per mu g DNA) in evct supernatants contained 10-20% hCG-H. In situ, hCG-H immunostaining was strong in invasive and endovascular evct, weaker in mononucleated villous cytotrophoblasts, but negative in the syncytiotrophoblast. In maternal sera, hCG-H concentrations continuously decreased during pregnancy from 406 +/- 222 ng/ml at 9 WG to 8 +/- 6 ng/ml at 19 WG, whereas total hCG picked up at 11 WG and then decreased. Conclusions: This study suggests that the high levels of hCG-H observed in first-trimester maternal sera are mainly from invasive evct origin, reflecting the early trophoblast invasion process. (J Clin Endocrinol Metab 95: E240-E244, 2010)