Defect of villous cytotrophoblast differentiation into syncytiotrophoblastin Down's syndrome

The syncytiotrophoblast (ST) is one of the major components of the human pl acenta, as it is involved in fete-maternal exchanges and the secretion of p regnancy-specific hormones. The aim of this study was to elucidate the form ation and function of the ST in trisomy 21 (Down's syndrome). We first used the in vitro model of cytotrophoblast differentiation into ST. Cytotrophob lasts were isolated from 15 trisomy al-affected placentas (12-35 weeks gest ation) and 10 gestational age-matched control placentas. In vitro cytotroph oblasts isolated from normal placenta fused to form the ST. This was associ ated with an increase in transcript levels and in the secretion of hCG, hum an placental lactogen, placental GH, and leptin. In trisomy 21-affected pla centas, we observed a defect (or a delay) in ST formation and a dramatic de crease in the synthesis and secretion of these hormones compared to those i n 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 al-affected placentas compared to controls. T hese results will be of help in understanding the maternal hormonal markers of fetal trisomy 21 and the consequences of placental defects for fetal de velopment.