Evidence for regulation of the complement system during pregnancy being ancient and conserved in mammals.

Here we demonstrate that regulation of the Complement (C') components of the immune system is an ancient and conserved feature of mammalian pregnancy. Transcript levels were reduced for complement components C3 and C4 throughout pregnancy in a marsupial, Monodelphis domestica. Downstream C' component transcripts were significantly less abundant relative to non-pregnant controls at the start of pregnancy but increased during late pregnancy, in some cases peaking close to parturition. These results are consistent with observations in human pregnancy that deposition of C5 through C9 on fetal membranes is associated with labor and parturition. Complement regulators CD46 and CD59 are present at the fetomaternal interface during M. domestica pregnancy as well, implying regulation of C' effector mechanisms is necessary for maintenance of normal marsupial pregnancy. Collectively these results support regulating the complement system may have contributed to the transition from oviparity to viviparity in mammals over 165 million years ago.