Abnormal villus trophoblast differentiation and placental thrombosis. Progenitor cytotrophoblasts proliferate (1) and divide asymmetrically (2 and 3) so that the progenitor is conserved (4) for subsequent rounds of syncytial fusion. The daughter cytotrophoblast prepares for syncytial fusion (5), focally donating transcriptional machinery and antiapoptotic proteins into the outer syncytiotrophoblast (6). Syncytial nuclei gradually progress toward apoptosis and aggregate in syncytial knots (7 and 8). Syncytial fusion is restricted in severe PE, increasing the number and size of syncytial knots (9 and 10). Some knots may fragment into the intervillous space, whereas other parts of the abnormal villi have exposed cytotrophoblasts and basal lamina (11) that trigger local thrombosis (see inset). Syncytiotrophoblast fragments are filtered in the maternal lungs, whereas microparticles pass through and may exert systemic effects in the maternal vasculature.