Pre-eclampsia is a pregnancy complication characterized by defective vascular
remodeling in maternal decidua responsible for reduced blood flow leading to functional
and structural alterations in the placenta. We have investigated the contribution of the
complement system to decidual vascular changes and showed that trophoblasts
surrounding unremodeled vessels prevalent in preeclamptic decidua fail to express C1q
that are clearly detected in cells around remodeled vessels predominant in control
placenta. The critical role of C1q is supported by the finding that decidual trophoblasts
of female C1qa-/- pregnant mice mated to C1qa+/+ male mice surrounding remodeled
vessels express C1q of paternal origin. Unlike C1qa-/- pregnant mice, heterozygous
C1qa+/- and wild type pregnant mice share a high percentage of remodeled vessels. C1q
was also found in decidual vessels and stroma of normal placentae and the staining was
stronger in preeclamptic placentae. Failure to detect placental deposition of C1r and C1s
associated with C1q rules out complement activation through the classical pathway.
Conversely, the intense staining of decidual endothelial cells and villous trophoblast for
ficolin-3, MASP-1 and MASP-2 supports the activation of the lectin pathway that
proceeds with the cleavage of C4 and C3 and the assembly of the terminal complex.
These data extend to humans our previous findings of complement activation through the
lectin pathway in an animal model of pre-eclampsia and provide evidence for an important
contribution of C1q in decidual vascular remodeling.
