The role of apoptosis in human embryo implantation

Abstract

The process of embryo attachment and invasion through the endometrial epithelial cells and subsequent implantation into the decidualized endometrial stroma is the groundbreaking step for the establishment of a successful pregnancy. Necessary prerequisites are a receptive endometrium, a good-quality embryo and a well-orchestrated molecular dialog between embryo and maternal endometrium. The embryo–maternal dialog is conducted via a wide scope of factors, including secreted cytokines, chemokines, and growth factors in addition to the expression of corresponding receptors and co-receptors. Several embryonic proteins, including the aforementioned, are involved in the process of apoptosis, which necessarily needs to take place at the maternal endometrium to allow the embryo to invade. The endometrial epithelium is thereby disintegrated completely within a particular area, whereas the endometrial stroma seems to require a more depth-limited apoptosis. As of today, the exact mechanisms and factors mediating the apoptotic process involved in those apparently differently regulated incidents are not fully understood, particularly with regard to stromal cell apoptosis. There is evidence though, that cytokines and their respective receptors play a major role. A suggested important co-receptor for cytokines, which is highly upregulated in the receptive human endometrium, is the heparan sulfate proteoglycan syndecan-1. It is present on the cell surface and involved in the regulation of cell–cell-interaction, cell binding, cell signaling and cytoskeletal organization and therefore represents a possible mediator of apoptosis regulation in human endometrium. Herein, the literature on endometrial epithelial and stromal apoptosis in general, and in light of the influence of syndecan-1, is reviewed.