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).