Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond

Abstract

The complement cascade was identified over 100 years ago, yet investigation of its role in pregnancy remains an area of intense research. Complement inhibitors at the maternal-fetal interface prevent inappropriate complement activation to protect the fetus. However, this versatile proteolytic cascade also favorably influences numerous stages of pregnancy, including implantation, fetal development, and labor. Inappropriate complement activation in pregnancy can have adverse lifelong sequelae for both mother and child. This review summarizes the current understanding of complement activation during all stages of pregnancy. In addition, consequences of complement dysregulation during adverse pregnancy outcomes from miscarriage, preeclampsia, and pre-term birth are examined. Finally, future research directions into complement activation during pregnancy are considered.

Changes in Expression of Complement Components in the Ovine Spleen during Early Pregnancy

“…The activity of the complement system is enhanced systemically during pregnancy, but the activity is inhibited at the placenta for pregnancy maintenance [ 3 ]. Complement regulation is necessary for a successful pregnancy, and some complement components are favorable in the normal fetal growth at the stage of pre-implantation to placentation [ 4 ]. However, during early pregnancy, complement regulation in the spleen is unclear in ewes.…”

CFP is a prognostic biomarker and correlated with immune infiltrates in Gastric Cancer and Lung Cancer

“…Related clinical data had shown that complement activation is at least partially involved in the progression of non-small cell lung cancer [15]. Several recent studies also confirmed that complement plays an active role in regulating T cell immunity [16,17] and natural killer cells are also bound to CFP through NKp46 receptor [18]. CFP is an important positive regulator of alternative pathway (AP) which acts to stabilize C3 and C5 invertase, and is associated with the destruction of bacteria, neutralization of viruses, and cytolysis of certain red blood cells, and as an important component of the complement substitution activation pathway [19].…”

Low Preconception Complement Levels Are Associated with Adverse Pregnancy Outcomes in a Multicenter Study of 260 Pregnancies in 197 Women with Antiphospholipid Syndrome or Carriers of Antiphospholipid Antibodies

“…Unfortunately, findings emerging in different studies are not always easily comparable: complement determinations were performed in different weeks of gestation and it is well known that pregnancy itself exerts an important influence on the complement components synthesis [20][21][22][23]. Heterogeneity refers even to clinical criteria for study inclusion, with some studies enrolling exclusively women with primary APS and others also women with systemic autoimmune rheumatic conditions.…”