Reconsidering the Medawar paradigm placental viviparity existed for eons, even in vertebrates; without a "problem": Why are Tregs important for preeclampsia in great apes?

The classic Medawar paradigm sees viviparity in vertebrates as a "problem". Established in 1953, it was then largely determined by a self-non-self view of the immune system. However, there are alternative models of the immune system, such as the danger model. For these models, pregnancy is neither a problem nor a danger. Supporting this view, we recall that placenta or placental-like-dependent(1) (allo) pregnancy has existed for eons. In fact, it appeared as far back as the time of aquatic colony invertebrates, such as some of the Bryozoa.(2) Since then, convergent evolution has seen placentation appear in a large variety of phyla. These placentae did not seem to cause "immunological problems", even in vertebrates possessing a graft rejection potential. The reappearance of placentae in marsupial and eutherian mammals found placentae confronted with a highly developed adaptive immune system. Two strategies were developed, therefore: short-term only placentation (marsupials) or specialised control of T cell-mediated immunity (Tregs). The problem is likely to be most acute in cases of deep invasive placentation. As an alternative to a restricted view of the Medawar paradigm for preeclampsia, an integrated model putting both inflammation and Tregs into perspective is proposed, somehow embedding the questioning of the initial Medawar paradigm.