Inefficient development of syncytiotrophoblasts in the Atp11a -deficient mouse placenta

Significance Plasma membranes are composed of a lipid bilayer in which phosphatidylserine (PtdSer) is confined to the inner leaflet by the action of flippase that translocates PtdSer from the outer to inner leaflets. Two P4-ATPases (ATP11A and ATP11C) work as flippase at plasma membranes. Here, we report that the mouse placenta expresses only ATP11A, and Atp11a- deficient mouse embryos die during embryogenesis due to inefficient formation of syncytiotrophoblasts in the placental labyrinth. The flippase-null mutation inactivates human choriocarcinoma BeWo cells to translocate PtdSer into the inner leaflet and undergo cell fusion. These findings highlight the importance of flippase to regulate the distribution of phospholipids for cell fusion, at least in trophoblast fusion.