The complement system in the pathophysiology of pregnancy

Area of Science:

• Immunology
• Reproductive Biology
• Complement System

Background:

• The placenta possesses an active complement system for protection against pathogens.
• Semi-allogeneic fetal tissues and maternal alloantibodies can trigger complement-mediated immune attack at the feto-maternal interface.
• Uncontrolled complement activation poses a risk of fetal loss, growth restriction, or death.

Purpose of the Study:

• To investigate the role of the complement system in placental immunity.
• To examine the protective mechanisms against complement-mediated attack during pregnancy.
• To analyze the involvement of the complement system in fetal damage induced by anti-phospholipid antibodies in a mouse model.

Main Methods:

• Analysis of complement system components in placental tissue.
• Evaluation of complement regulatory proteins (DAF, MCP, CD59) on trophoblasts.
• Assessment of embryonic lethality in mice deficient in complement regulator Crry.
• Investigation of fetal damage in a mouse model of anti-phospholipid antibody-induced complications.

Main Results:

• Regulatory proteins DAF, MCP, and CD59 on trophoblasts prevent uncontrolled complement activation.
• Absence of complement regulators leads to embryonic lethality in mice, highlighting their critical role.
• Excessive complement activation in the placenta is linked to fetal growth restriction and demise.

Conclusions:

• The complement system is crucial for placental defense but requires strict regulation.
• Deficiency in complement regulatory proteins compromises pregnancy outcomes.
• Understanding complement's role is vital for addressing pregnancy complications like those induced by anti-phospholipid antibodies.