Impact of trisomy 21 on human trophoblast behaviour and hormonal function.
Although trisomy 21 (T21) is the most frequent genetic abnormality and some maternal serum markers for this fetoplacental aneuploidy are of placental origin, little is known of its impact on placental development. We therefore studied the influence of T21 on trophoblast behaviour. Using cultured cells from 46 human T21 pregnancies, we confirmed the defective morphological and functional differentiation of the villous cytotrophoblast in this setting; indeed, villous cytotrophoblast cells aggregate normally but fuse inefficiently to form the syncytiotrophoblast. This is in part related to the abnormal oxidative status of the T21 cytotrophoblast, characterized by a gene dosage-related increase in SOD-1 (copper-zinc superoxide dismutase) expression and activity. This was associated with a significant (P < 0.01) increase in catalase activity but no significant change in glutathione peroxidase activity. On the basis of these in vitro findings and studies of large panels of maternal serum, we propose a pathophysiological explanation for trisomy 21 maternal serum markers of placental origin.
Pidoux
G
G
INSERM U427, Faculté des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l'Observatoire, 75270 Paris, France.
Guibourdenche
J
J
Frendo
J-L
JL
Gerbaud
P
P
Conti
M
M
Luton
D
D
Muller
F
F
Evain-Brion
D
D
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002374:Catalase / Q000378:metabolism; D002449:Cell Aggregation; D002459:Cell Fusion; D002478:Cells, Cultured; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D002824:Chorionic Villi / Q000473:pathology; D004314:Down Syndrome; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000097:blood*; D011247:Pregnancy / Q000097:blood*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D020738:Leptin; C000606290:SOD1 protein, human; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1