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

Abstract

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-dependent11For a great number of authors, placenta is a term (to be) used only for placental mammals. Thus, many authors use the term “placenta-like structure” when dealing with non-eutherian animals (excluding thus the use of “placenta” even when speaking of non-eutherian animals (e.g. even for the early embryonic stages of marsupials). However, others define the placenta as “a temporary organ that joins the mother and the foetus, transferring oxygen and nutrients". Hence, many zoologists speak of placentae for a variety of non-mammalian species. This terminology is used throughout this article, as interfacing may pose “immunological problems”. (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.22Moss animals, aquatic colonial invertebrates, also known as Ectoprocta, appearing in the early Ordovician period, and still present. 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.