The key components required to initiate molecular interactions between the endometrium and blastocysts have been shown to be present in the apical surface of the endometrium. Previous studies have reported that the L-selectin adhesion system, comprising of L-selectin and its oligosaccharide ligands, could be regarded as one of the vital pathways mediating these preliminary interactions. A recent research is proposed to be the first to demonstrate subcellular localization of L-selectin ligand MECA-79 at pinopodes, the apical most surface of the receptive endometrium, and the first materno-fetal contact region. The study suggests that pinopodes probably induce a shear-stress-dependent tethering-type adhesion during the initial phase of embryo implantation.
Reza Nejatbakhsh from the Shaheed Beheshti University of Medical Sciences, Tehran, Iran, and coworkers, investigated the subcellular distribution pattern of MECA-79 in the apical region of the endometrium during the implantation window. Endometrial biopsies were obtained during the secretory phases from fertile women in the age group of 25 to 42 years. These biopsies were evaluated using various approaches such as scanning electron microscopy (SEM), immunoblotting, immunostaining for light microscopy and transmission electron microscopy (TEM), and statistical analysis of the area-related numerical densities of immunoreactive MECA-79-bound nanogolds. The study is published in the journal Reproductive Biology and Endocrinology.
The midluteal phase samples demonstrated abundant fully developed pinopodes amidst a few regressing ones, as per SEM results. According to the findings of immunofluorescent staining, immunoblotting, and HRP-immunostaining, the specimens also showed the expression of MECA-79. TEM results revealed that MECA-79 was expressed in pinopodes in the midluteal phase with a greater area-related numerical density when compared to pinopode-free regions. Furthermore, MECA-79 was localized at the glandular and luminal epithelium, mainly at the cell membrane, with minimal cytoplasmic staining. The stroma, however, did not demonstrate MECA-79 immunostaining.
Pinopodes, the bleb-like, hormone-dependent, integrin-enriched subcellular structures appear during implantation and extend ahead of the glycocalyx layer of apical membrane of the endometrial epithelium. They morphologically resemble the docking structures of the endothelium that are considered vital to initiate molecular interactions to capture the leukocyte. It appears logical to speculate that similar to the L-selectin mediated lymphocyte movement over the endothelial cells, the blastocyst rolls over the glycocalyx of the endometrial epithelium through weak interactions with L-selectin. The rolling mediated by L-selectin may enable a crosstalk between the maternal epithelia and blastocyst, resulting in stronger cell adhesion through direct binding of the constituents in the plasma membranes on the maternal and fetal sides.
The current study proposes a novel role for pinopodes in the cell-to-cell interactions occurring during the initial stages of embryo-endometrial apposition and adhesion, identical to the tethering process of blood cells; however, further large trials are mandatory to validate the same.
1. Nejatbakhsh R, Kabir-Salmani M, Dimitriadis E, et al. Subcellular localization of L-selectin ligand in the endometrium implies a novel function for pinopodes in endometrial receptivity. Reprod Biol Endocrinol. 2012 Jun 15;10(1):46.