Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy hCG and Down Syndrome

• Published in: The journal of clinical endocrinology and metabolism Vol. 89; no. 2; pp. 727 - 32
• Main Authors: Frendo, Jean-Louis, Guibourdenche, Jean, Pidoux, Guillaume, Vidaud, Michel, Luton, Dominique, Giovangrandi, Yves, Porquet, Dominique, Muller, Françoise, Evain-Brion, Danièle
• Format: Journal Article
• Language: English
• Published: Endocrine Society 01.02.2004
• Subjects: Antigens, CD; Cells, Cultured; Chorionic Gonadotropin; Culture Media; Down Syndrome; Endocrinology and metabolism; Female; Fucosyltransferases; Glycosylation; Human health and pathology; Humans; Leydig Cells; Life Sciences; Male; Pregnancy; Progesterone; Reproductive Biology; RNA, Messenger; Trophoblasts; cell fusion; placenta; trophoblast; hCG
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-030668

Total human chorionic gonadotropin (hCG) is high in maternal serum at 14-18 wk of trisomy 21 (T21)-affected pregnancy, despite low placental hCG synthesis. We sought an explanation for this paradox. We first observed that, in T21-affected pregnancies, maternal serum hCG levels peaked at around 10 wk and then followed the same pattern throughout pregnancy as in controls, albeit at a higher (2.2-fold) level. After delivery, hCG clearance was not significantly different from that in controls. We isolated cytotrophoblasts from 29 T21-affected placentas (12-25 wk) and 13 gestational age-matched control placentas and cultured them for 3 d. In this large series, we confirmed that, in the culture medium of trophoblasts isolated from T21 placentas, hCG secretion was significantly lower (P < 0.003) than in controls, in contrast to the high hCG in maternal serum of the same patients. In T21 cultured trophoblasts, transcripts of sialyltransferase-1 and fucosyltransferase-1 were abnormally high. In corresponding culture medium, hCG was abnormally glycosylated; highly acidic [isoelectric points (pHi) = 4.5] as shown by isoelectric focusing, immunoblotting, and lectin binding; and weakly bioactive (46% of control) as determined using the Leydig cell model. In conclusion, T21 trophoblast cells produced hCG that was weakly bioactive and abnormally glycosylated but whose maternal clearance was unaltered.