Figure 2: Both complement deficiency and complement over-activation can lead placenta damage. (A) Trophoblast cells invading the maternal decidua is accompanied by a large number of apoptotic cell and tissue debris in normal placenta. These apoptotic cells are quickly cleared by phagocytes without inducing immune activation. (B) In one situation , complement over-activation promotes neutrophil recruitment, mediates the release of inflammatory cytokines, and activates the adaptive immune system to jointly induce placental damage. Trophoblast cell invasion ability decline, and their apoptosis and necrosis are accelerated, a large amount of tissue debris enter the circulating blood, and spiral artery remodeling is obstructed. At the same time, complement-mediated hypercoagulation leads to local microthrombosis and the following fetal ischemia and hypoxia, forming a “second hit” to pregnancy. In another situation , complement deficiency leads to the accumulation of apoptotic and necrotic cells in the placenta. These apoptotic and necrotic cells activate the inflammatory signaling pathways to provoke inflammatory responses, like neutrophil recruitment and adaptive immune activation, and induce placental malformation and dysfunction. The pathological manifestations of the placenta are similar to the previous ones (complement over-activation(B)). Extravillous trophoblast (EVT); Cytotrophoblast (CyT); Syncytial trophoblast (SynT); Fetal blood vessels (FV); Neutrophil (N); Macrophages (Mφ); Monocytes (Mo); lymphocytes (L); Dendritic cells (DC).