Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy.
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.
Frendo
J-L
JL
Institut National de la Santé et de la Recherche Médicale, U 427, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 75270 Paris, France.
Guibourdenche
J
J
Pidoux
G
G
Vidaud
M
M
Luton
D
D
Giovangrandi
Y
Y
Porquet
D
D
Muller
F
F
Evain-Brion
D
D
D015703:Antigens, CD / Q000235:genetics; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000096:biosynthesis* / Q000097:blood; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D011247:Pregnancy / Q000097:blood / Q000378:metabolism*; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012799:Sialyltransferases; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D000097631:Galactoside 2-alpha-L-fucosyltransferase; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D015703:Antigens, CD; D006063:Chorionic Gonadotropin; D003470:Culture Media; D005647:Fucosyltransferases; D011374:Progesterone; D012333:RNA, Messenger; D012799:Sialyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase