Trophoblast-uterine interactions at implantation

Abstract

Implantation of the embryo in the uterus is a critical and complex event and its failure is widely considered an impediment to improved success in assisted reproduction. Depending on whether placentation is invasive or superficial (epitheliochorial), the embryo may interact transiently or undergo a prolonged adhesive interaction with the uterine epithelium. Numerous candidate interactions have been identified, and there is good progress on identifying gene networks required for early placentation. However no molecular mechanisms for the epithelial phase are yet firmly established in any species. It is noteworthy that gene ablation in mice has so far failed to identify obligatory initial molecular events.

Figure 1

Diagrammatic representation of the series of interactions between the trophectoderm/trophoblast (TE) and luminal epithelium (LE) and subjacent stroma. Potential roles of cell adhesion molecules at each stage are indicated. 1) Pre-receptive polarised endometrial epithelium with desmosomes distributed along lateral LE cell surfaces and non-adhesive apical cell surface; 2) Receptive endometrium and initial embryo attachment: reorganisation of lateral LE adhesion complexes accompanies apical carbohydrate ligand engagement to tether blastocyst; integrins and cell–bound HB-EGF now become available for TE-binding; 3) Stabilisation of initial attachment by αv or other integrin-mediated adhesion involving bridging ligands shown; other components are also probably functional; 4) Potential signalling through cell adhesion ligand-receptor interaction including calmodulin and calcium.