The complement system at the embryo implantation site

The Complement (C) system plays an important role in the control of infectious agents and in the removal of immune complexes and apoptotic cells. Like other components of innate immunity, C is able to recognize the targets through the early components and to attack them through the biologically active products released as a result of activation. While recognition is restricted to harmful agents, the effector phase associated with the activation products of the terminal components is not selective for foreign targets and may also attack host cells. Thus, C can be considered an effective defence system but also a potential danger that may differently affect various tissues and organs. The protective function of the C system is particularly important during pregnancy since the implanted embryo is vulnerable to attack by pathogens that colonize the cervico-vaginal cavity. Uncontrolled complement activation is prevented in successful pregnancy by the regulatory proteins positioned on the surface of several placental cells, however, unrestricted C activation induced by antibody-dependent and independent mechanisms may overcome the neutralizing effect of the C inhibitors and results in tissue damage and poor pregnancy outcome. C components produced at feto-maternal interface serve an important function in placental development. C1q synthesized by decidual endothelial cells and expressed on the cell surface is particularly important in this regard because it acts as a molecular bridge between endovascular trophoblast and endothelial cells. C1q is also produced by trophoblast and is used to favour trophoblast migration through the decidua. Defective expression of C1q by trophoblast is associated with impaired trophoblast invasion of decidua and may have important implications in pregnancy disorders such as preeclampsia characterized by reduced vascular remodeling. In conclusion the C system behaves as a double-edged sword, exerting a protective function and inducing damage in pathological situations that may result in poor pregnancy outcome.