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

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.
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https://www.hal.inserm.fr/inserm-00128419
Contributor : Jean-Louis Frendo Connect in order to contact the contributor
Submitted on : Monday, February 12, 2007 - 1:48:11 PM
Last modification on : Thursday, December 10, 2020 - 4:04:03 PM
Long-term archiving on: : Tuesday, April 6, 2010 - 10:57:56 PM

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Jean-Louis Frendo, Jean Guibourdenche, Guillaume Pidoux, Michel Vidaud, Dominique Luton, et al.. Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy.: hCG and Down Syndrome. Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2004, 89 (2), pp.727-32. ⟨10.1210/jc.2003-030668⟩. ⟨inserm-00128419⟩

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