Uterine remodelling in marsupial pregnancy: implications for mammalian placental evolution

Abstract

Amniote viviparity requires remodelling of the uterus for placentation and successful embryonic development. Similar remodelling during pregnancy in eutherian mammals, viviparous squamate reptiles, and in the marsupial Sminthopsis crassicaudata, suggest that viviparous amniotes share a common beginning to pregnancy, yet variable molecular patterns in different taxa suggest that remodelling evolves via flexible pathways. Hence, comparison of remodelling during pregnancy across viviparous amniote groups can identify key evolutionary mechanisms and drivers of viviparity. Here I test the generality and importance of uterine remodelling in marsupial pregnancy by investigating uterine alterations during pregnancy across the major marsupial phylogenetic groups and placental types- Sminthopsis crassicaudata (Dasyuridae), Monodelphis domestica (Didelphidae), Trichosurus vulpecula (Phalangeridae), and Macropus eugenii (Macropodidae). Using both scanning and transmission electron microscopy, I show that uterine epithelial cells of these species undergo substantial morphological remodelling during pregnancy that is likely ubiquitous in marsupials. I provide support for the theory that non-invasive placentation is secondarily derived in marsupials by showing that M. eugenii and T. vulpecula undergo unique uterine adaptations that differ from those of M. domestica, a member of the least derived living group, Didelphidae. I use Western blotting and immunofluorescence microscopy to show that key molecules of eutherian pregnancy, including talin, paxillin and desmoglein-2, underpin uterine remodelling in marsupials, yet are co-opted to perform unique roles. Lastly, I show that the uterus undergoes molecular reinforcement in marsupial pregnancy that may regulate embryonic invasion. My findings suggest that remodelling of the uterine epithelium in marsupials enables greater maternal control over pregnancy and is likely shaped by intra-uterine conflict between mother and embryo.