Uterine changes during mammalian pregnancy and the evolution of placentation

Abstract

Reproduction is a complex phenomenon that is fundamental to all living things. There is a plethora of strategies that animals utilise to reproduce. The uterine epithelium of viviparous mammals undergoes vast remodelling to accommodate the developing embryo. There are several levels of placental invasion in mammals that develop a placenta, based on the number of cell layers that separate the developing fetus and maternal blood stream. This thesis investigated whether there are common molecular changes to the uterine surface during pregnancy in Theria. I compared uterine remodelling across several phylogenetic groups with independent origins of endotheliochorial placentae to determine how this placenta type evolved. I tested the generality of uterine remodelling during pregnancy in the marsupial, Sminthopsis crassicaudata (Dasyuridae; the fat-tailed dunnart) and the eutherian, Felis catus (Felidae; the domestic cat) and Dipodomys merriami (Heteromyidae; Merriam’s kangaroo rat). I used Transmission and Scanning Electron Microscopy to study the ultrastructural changes to the uterine epithelium during pregnancy. I used immunofluorescence microscopy and Western blotting to show that there are common changes to the distribution of key lateral adhesion molecules, desmoglein-2 and E-cadherin to facilitate the formation of the placenta. I confirmed that desmosomes and the adherens junction redistribute and break down at attachment during marsupial pregnancy. I also showed that the same ultrastructural and molecular changes to the uterine epithelium are seen in eutherian species which represent separate lineages of endotheliochorial placentation. I was the first to identify a plasma membrane transformation during pregnancy in Dipodomys merriami, a rodent species which represent a recent evolution of endotheliochorial placentation within Rodentia. I determined the effect of the reproductive hormones, progesterone and 17β-oestradiol on the reproductive tract of Sminthopsis crassicaudata, concluding that the plasma membrane transformation is regulated by the same hormonal mechanisms among therian species. The conclusions from this thesis support the theory that uterine remodelling and the plasma membrane transformation are crucial for successful pregnancy in viviparous mammals with commonalities in molecular and morphological changes among species.