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Trophoblast Production of a Weakly Bioactive Human Chorionic Gonadotropin in Trisomy 21-Affected Pregnancy

Institut National de la Santé et de la Recherche Médicale, U 427 (J.-L.F., J.G., G.P., D.E.-B.), Laboratoire de Génétique Moléculaire (Y.G., M.V.), Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 75270 Paris, France; and Service de Gynécologie Obstétrique (D.L.) and Service d’Hormonologie (J.G., D.P., F.M.), Hôpital Robert Debré, 75019 Paris, France

Address all correspondence and requests for reprints to: Danièle Evain-Brion, Institut National de la Santé et de la Recherche Médicale, U 427, Faculté de Pharmacie, 4, Avenue de l’Observatoire, 75270 Paris, France. E-mail: evain{at}pharmacie.univ-paris5.fr.

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.

This work was supported by la Caisse d’Assurance Maladie des Professions Libérales Province, l’Association Française pour la Recherche sur la Trisomie 21, la Fondation pour la Recherche Médicale (ARS 2000), and by a grant from Institut National de la Santé et de la Recherche Médicale (Projet Avenir).

J.-L.F. and J.G. contributed equally to this work.

Abbreviations: hCG, Human chorionic gonadotropin; IEF, isoelectrofocusing; MoM, multiples of the median; pHi, isoelectric point; T21, trisomy of chromosome 21.

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