Impaired function of trophoblast cells derived from translocated hESCs may explain pregnancy loss in women with balanced translocation (11;22).
PURPOSE
The aim of the study was to study whether the trophoblasts carrying unbalanced translocation 11,22 [t(11;12)] display abnormal expression of trophoblastic genes and impaired functional properties that may explain implantation failure.


METHODS
t(11;22) hESCs and control hESCs were differentiated in vitro into trophoblast cells in the presence of BMP4, and trophoblast vesicles (TBVs) were created in suspension. The expression pattern of extravillous trophoblast (EVT) genes was compared between translocated and control TBVs. The functional properties of the TBVs were evaluated by their attachment to endometrium cells (ECC1) and invasion through trans-well inserts.


RESULTS
TBVs derived from control hESCs expressed EVT genes from functioning trophoblast cells. In contrast, TBVs differentiated from the translocated hESC line displayed impaired expression of EVT genes. Moreover, the number of TBVs that were attached to endometrium cells was significantly lower compared to the controls. Correspondingly, invasiveness of trophoblast-differentiated translocated cells was also significantly lower than that of the control cells.


CONCLUSIONS
These results may explain the reason for implantation failure in couple carriers of t(11;22). They also demonstrate that translocated hESCs comprise a valuable in vitro human model for studying the mechanisms underlying implantation failure.
['Shpiz|Alina|A|', 'Ben-Yosef|Dalit|D|', 'Kalma|Yael|Y|']
D000028:Abortion, Induced D000022:Abortion, Spontaneous D000328:Adult D002454:Cell Differentiation D010064:Embryo Implantation D004717:Endometrium D005260:Female D000066449:Human Embryonic Stem Cells D006801:Humans D010920:Placenta D011247:Pregnancy D011261:Pregnancy Trimester, First D014178:Translocation, Genetic D014327:Trophoblasts
Trophoblasts Translocation Implantation Human embryonic stem cells