Part K: Pathophysiology of the Complement System at Feto-Maternal Interface
Pp. 422-434 (13)
Roberta Bulla, Chiara Agostinis and Francesco Tedesco
The early phase of pregnancy is characterized by an inflammatory-like process and vascular remodeling that occur in decidua and are associated with hormonal changes. Extravillous trophoblast and NK cells present in decidua are responsible for these changes that are also contributed by the complement system. Complement activation occurs in physiologic pregnancy at decidual level as a result of tissue remodeling. Soluble and cell surface expressed complement regulators protect decidual endothelial cells (DECs) and trophoblast from complement attack that may lead to tissue damage in normal pregnancy. The recent report that preeclampsia is associated with mutations in the genes encoding for some of the complement inhibitors supports the important role of these proteins in the protection of the feto-placental unit. Control of complement activation can easily be overcome in the presence of complement-fixing antibodies directed against β2-glycoprotein I responsible for fetal loss and growth restriction.
Complement components synthesized by several decidual cells including trophoblast, DECs, and macrophages serve a defense function against infectious agents and promotes the removal of apoptotic cells. More, the complement system was recently found to contribute to placental development. Particularly important in this regard is C1q which is expressed on the surface of DECs and acts favoring the adhesion of endovascular trophoblast to the endothelial cells. Extravillous trophoblast is another source of C1q which binds to extracellular matrix and promotes trophoblast migration through the decidua. Unremodeled spiral arteries are surrounded by trophoblast cells that manifests reduced expression of C1q with important implications in preeclampsia characterized by reduced vascular remodeling.
C, C1q, C7, inflammation, placenta, pregnancy disorders.
Department of Life Sciences, University of Trieste, Trieste, Italy.