Involvement of the HERV-derived cell-fusion inhibitor, suppressyn, in the fusion defects characteristic of the trisomy 21 placenta.
Suppressyn (SUPYN) is the first host-cell encoded mammalian protein shown to inhibit cell-cell fusion. Its expression is restricted to the placenta, where it negatively regulates syncytia formation in villi. Since its chromosomal localization overlaps with the Down syndrome critical region and the TS21 placenta is characterized by delayed maturation of cytotrophoblast cells and reduced syncytialization, we hypothesized a potential link between changes in SUPYN expression and morphologic abnormalities in the TS21 placenta. Here we demonstrate that an increase in chromosomal copy number in the TS21 placenta is associated with: (1) reduced fusion of cytotrophoblast cells into syncytiotrophoblast in vivo, (2) increased SUPYN transcription, translation and secretion in vivo, (3) increased SUPYN/syncytin-1 receptor degradation in vivo, (4) increased SUPYN transcription and secretion ex vivo, (5) decreased cytotrophoblast cell fusion ex vivo, and (6) reciprocal response of changes in SUPYN and CGB in TS21 placental cells ex vivo. These data suggest direct links between immature placentation in Down syndrome and increased SUPYN. Finally, we report a significant increase in secreted SUPYN concentration in maternal serum in women with pregnancies affected by Down syndrome, suggesting that SUPYN may be useful as an alternate or additional diagnostic marker for this disease.
Sugimoto, J; Schust, DJ; Yamazaki, T; Kudo, Y
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