Molecular and hormonal studies on molecules involved In the maintenance of uterine epithelial polarity in the rat

Abstract

Polarised epithelial cells are characterised by the organisation of the plasma membrane lipids and proteins into distinct domains. All these domains undergo many changes during the transition from a non-receptive uterine epithelial cell to one that is receptive to blastocyst implantation, despite the changes that these cells undergo they still retain a polarised epithelial phenotype. Several aspects of cell polarity were investigated in this thesis. Caveolin and cavin proteins were investigated to understand their involvement in membrane curvature as well as membrane lipid and cholesterol polarity. Junctional complexes were studied through the localisation and expression of afadin in UECs during early pregnancy. Filamin A (FLNA), an actin crosslinking protein was studied to understand the role that the actin cytoskeleton plays in the maintenance of cell polarity. At the time of implantation when a number of structures are altered or absent, the apical plasma membrane is rigid due to the elevated membrane cholesterol and FLNA associated actin networks, while the basolateral plasma membrane is less rigid, enabling caveolae formation. Afadin at this time is associated with the tight junction, where it may maintain distinct apical and basolateral domains. The findings of this thesis contribute to our understanding of uterine receptivity.