Trophoblast syncytialization maintains the placenta-heart axis

The developmental connection between the placenta and certain embryonic organs, such as the heart, is associated with normal pregnancy and complications, but how the placenta governs embryonic cardiogenesis is poorly understood. Trophoblasts fuse into a multinucleated syncytiotrophoblast (SynT) layer, primarily consisting of a placental materno-fetal interface. We identify that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is essential for trophoblast differentiation and fusion into SynT in human trophoblasts and mouse placentas. Moreover, SynT-derived PIBF1 enables the communication between SynT and adjacent vascular cells to develop the vascular network in the primary placenta and further impacts the early development of the embryonic cardiovascular system in an endocrine manner. Thus, SynT-derived factors and SynT itself in the placenta may play crucial roles in the proper organogenesis of other organs in the embryo. To verify the effect of rsPIBF on the development of hHO, on day 8 (one day after hHO induction), cells were cultured in the hHO medium (control group), or hHO medium containing 200 ng/ml sPIBF (sPIBF group), with the medium replaced every two days until day 19-21.