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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 10 3700-3707
Copyright © 2000 by The Endocrine Society


Original Studies

Defect of Villous Cytotrophoblast Differentiation into Syncytiotrophoblast in Down’s Syndrome1

J. L. Frendo, M. Vidaud, J. Guibourdenche, D. Luton, F. Muller, D. Bellet, Y. Giovagrandi, A. Tarrade, D. Porquet, P. Blot and D. Evain-Brion

INSERM, U-427 (J.L.F., A.T., D.B.-E.), Laboratoire de Génétique Moléculaire (M.V., Y.G.), Centre National de la Recherche Scientifique (D.B.), UPRES-A 8067, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 75270 Paris, France; Service d’Hormonologie (J.G., D.P.) and Service de Gynécologie Obstétrique (D.L., P.B.), Hôpital Robert Debré, 75019 Paris, France; and Service de Biochimie, Hôpital Ambroise Paré (F.M.), 92104 Boulogne, France

Address all correspondence and requests for reprints to: Dr. D. Evain-Brion, INSERM U-427, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l’Observatoire, 75270 Paris Cedex 06, France. E-mail: evain{at}pharmacie.univ-paris5.fr

The syncytiotrophoblast (ST) is one of the major components of the human placenta, as it is involved in feto-maternal exchanges and the secretion of pregnancy-specific hormones. The aim of this study was to elucidate the formation and function of the ST in trisomy 21 (Down’s syndrome). We first used the in vitro model of cytotrophoblast differentiation into ST. Cytotrophoblasts were isolated from 15 trisomy 21-affected placentas (12–35 weeks gestation) and 10 gestational age-matched control placentas. In vitro cytotrophoblasts isolated from normal placenta fused to form the ST. This was associated with an increase in transcript levels and in the secretion of hCG, human placental lactogen, placental GH, and leptin. In trisomy 21-affected placentas, we observed a defect (or a delay) in ST formation and a dramatic decrease in the synthesis and secretion of these hormones compared to those in cultured cells isolated from control age-matched placentas. These results were confirmed by a significant (P < 0.001) decrease in gene expression in total homogenates of trisomy 21-affected placentas compared to controls. These results will be of help in understanding the maternal hormonal markers of fetal trisomy 21 and the consequences of placental defects for fetal development.




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