Immunology of Implantation, Implantation Failure and Pregnancy. Part A: Regulators of Early Invasion of Trophoblast Cells

Controlled invasion of the trophoblast cells during early stages of embryonic development is one of the essential attributes leading to successful implantation. This involves two very crucial events i.e. initial attachment of the trophoblast cells to the maternal endometrium and later epithelial to mesenchymal transition of trophoblast cells leading to their dissociation from the cell column. These set of events are brought about by an orchestrated change in the expression of several adhesion molecules and the polar proteolytic degradation of the extra cellular matrix (ECM). A change in the expression of adhesion molecules like integrins, cadherins etc. helps in establishing close cell to cell association during the early phase of trophoblast attachment to the endometrial cells. Later, switch in their expression pattern enhances their interaction with the ECM components leading to an increase in the invasiveness of trophoblast cells. This is associated with an increase in the expression and activity of different kind of proteases along with a decrease in the expression of their physiological inhibitors. Additionally, mucin-type molecules like mucin 1 and podoplanin have also been shown to be involved in the regulation of trophoblast invasiveness. Expression of these effector molecules are regulated by the controlled expression of hormones, cytokines and growth factors of maternal as well as fetal origin. Further, enhancement of understanding about the molecular basis of regulation of early invasion at the feto-maternal interface by interplay of cytokines, adhesion molecules and proteases would help in improving the success rate of embryo implantation following assisted reproductive technologies.

Keywords: Blastocyst, Trophoblast cell, Invasion, Embryo implantation, Cytokine, Growth factor, Matrix metalloproteinase, Extracellular matrix, Admalysins, Tissue inhibitors of protease activity, Adhesion molecules, Integrin, Cadherin, Podoplanin, Mucin 1, Placenta, uPA, PAI.