Complement complicates pregnancies

During pregnancy, growth of new blood vessels into the placenta is required to nourish the developing fetus. On page 2165, Girardi et al. show that activation of the complement cascade blunts placental development by triggering the production of a potent angiogenesis inhibitor. Monitoring levels of complement activation in pregnant women might thus be useful in predicting pregnancy complications.

This group had previously shown that inhibition of complement activation prevented pregnancy loss in an antibody-dependent mouse model of miscarriage. But they understood neither what triggered complement activation nor how complement interfered with normal fetal development.

Girardi and colleagues now solve half the mystery in a model of spontaneous miscarriage. Complement activation, they show, triggers the production of a decoy receptor—soluble vascular endothelial growth factor receptor-1 (sVEGFR-1)—that sops up the vessel-building protein VEGF, which is needed to...