Complement regulation during pregnancy.

Complement has an important role in innate immunity and inflammation. Complement also has the capacity to attack self tissues. Cells are protected from the deleterious effects of complement. The Crry protein belongs to a family of molecules that regulates complement activation, protecting tissues from complement-mediated damage. To investigate the role of these molecules in vivo, Crry-/- mice were generated. Crry-/- mice did not survive pregnancy owing to abnormal complement deposition in the placenta through the alternative pathway. Tissue damage related to C5 (production of C5a and C5b-9) was not required. Removal of inflammatory cells did not affect the phenotype. This suggests new noninflammatory mechanisms of pregnancy failure that are dependent solely on C3. The major abnormality was a failure of blood vessel formation in the placenta, revealing an unsuspected C3 effect in the vascular development of this organ.