Complement C3 and IgM Deposition in Placental Ischemia‐induced Hypertension in Rat

Abstract

Preeclampsia is characterized by new onset hypertension, decreased placental perfusion and increased complement activation. While our previous work demonstrated the importance of complement activation, particularly activation products C3a and C5a, in placental ischemia-induced hypertension in rat, the site of activation and activation pathway involved are unclear. Hypothesis: Complement activation via classical pathway occurs in placenta coincident with placental ischemia-induced hypertension. On gestation day (GD)14, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP) resulting in increased blood pressure GD19. The role of classical complement pathway activation in placenta was assessed by determination of IgM and C3 deposition in GD19 placenta. Using anti-rat C3, anti-rat IgM or isotype control antibody followed by Texas-red conjugated secondary antibody, staining in placental frozen sections was graded as strongly positive, weakly positive or negative compared to staining of serial sections with isotype control. Placenta from 5 of 6 RUPP animals stained strongly positive for C3 whereas placenta from only 1 of 6 Sham animals stained weakly positive. Similarly, 5 of 6 RUPP animals demonstrated strongly positive IgM with 3 of 6 Sham animals weakly positive for IgM deposition. Overall these data indicate increased placental deposition of IgM and C3 following placental ischemia, suggesting placental ischemia-induced complement activation occurs via classical pathway. Supported by NIH HL109843, NIH P20GM103418.