Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy

J Clin Endocrinol Metab. 2004 Feb;89(2):727-32. doi: 10.1210/jc.2003-030668.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Cells, Cultured
  • Chorionic Gonadotropin / administration & dosage
  • Chorionic Gonadotropin / biosynthesis*
  • Chorionic Gonadotropin / blood
  • Culture Media / chemistry
  • Culture Media / pharmacology
  • Down Syndrome / metabolism*
  • Down Syndrome / pathology
  • Female
  • Fucosyltransferases / genetics
  • Galactoside 2-alpha-L-fucosyltransferase
  • Glycosylation
  • Humans
  • Leydig Cells / metabolism
  • Male
  • Pregnancy / blood
  • Pregnancy / metabolism*
  • Progesterone / antagonists & inhibitors
  • Progesterone / metabolism
  • RNA, Messenger / metabolism
  • Sialyltransferases
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology

Substances

  • Antigens, CD
  • Chorionic Gonadotropin
  • Culture Media
  • RNA, Messenger
  • Progesterone
  • Fucosyltransferases
  • Sialyltransferases
  • ST6GAL1 protein, human