Transcription of immune genes at the fetomaternal interface during pregnancy in a model marsupial, Monodelphis domestica.

Abstract The evolutionary challenge of nourishing an allogeneic conceptus in the presence of an adaptive immune system has intrigued immunologists since Sir Peter Medawar brought attention to the “fetal allograft problem” in the 1950s. Though much has been learned in reproductive immunology, it has largely been limited to eutherian mammals such as humans, mice, and mammalian livestock. Therians are the lineage of mammals that include both eutherians, or “placentals”, and marsupials. Though eutherians and marsupials diverged approximately 148 million years ago, the two lineages share a common viviparous ancestor. Therefore marsupials and eutherians likely share immunological traits during pregnancy. Previous RNA-Seq studies demonstrated increased transcription of immune genes in late, terminal pregnancy. However since the RNA-Seq data only represented one pregnancy time point, less than 24 hours until birth, it was unclear whether immune gene transcription should be attributed to pregnancy, implantation, or parturition. We expanded time points to target the last 144 hours of pregnancy during which both implantation and parturition occur in Monodelphis domestica. We examined the transcription of cytokines as well as complement and their regulators at the fetomaternal interface in pregnant opossums. We found a significant increase in transcription of cytokines in the last 24 hours of pregnancy and comparatively little transcription of cytokines at the time of implantation. There was also little transcription of some complement components throughout pregnancy, particularly those in the upstream cascade. Some downstream complement components trended toward increased transcription in the last 48 hours of pregnancy.