Redistribution of adhering junctions in human endometrial epithelial cells during the implantation window of the menstrual cycle

Abstract

The human uterine epithelium is characterised by remarkable plasticity with cyclic changes in differentiation that are controlled by ovarian steroid hormones to optimise conditions for embryo implantation. To understand whether and how cell-cell adhesion is affected, the localisation of junction proteins was studied throughout the menstrual cycle. Expression patterns were examined by immunofluorescence in 36 human endometrial specimens of different cycle stages. Antibodies against the desmosomal proteins desmoplakin 1/2 (Dp 1/2) and desmoglein 2 (Dsg 2), the adherens junction proteins E-cadherin and β-catenin and also the common junctional linker protein plakoglobin showed a strong subapical staining during the proliferative phase until the early luteal phase (day 20). In the mid- to late luteal phase, however, these junctional proteins redistributed over the entire lateral plasma membranes. In contrast, tight junction proteins (ZO-1, claudin 4) remained at their characteristic subapical position throughout the menstrual cycle. mRNA levels of Dp 1/2, E-cadherin and ZO-1 obtained by real time RT-PCR were not significantly changed during the menstrual cycle. The observed redistribution of desmosomes and adherens junctions coincides with the onset of the so called implantation window of human endometrium. We propose that this change is controlled by ovarian steroids and prepares the endometrium for successful trophoblast invasion.

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

“…Immunostaining for E-cadherin and beta-catenin revealed a subapical localization at the lateral membrane of the glandular epithelial cells during the late proliferative and early luteal phase which disappeared during the mid-to late-luteal phase [37]. Also here, no significant changes in mRNA levels in could be detected throughout the cycle [37,43].…”

“…As members of the tight junction complex, up to now, claudin-1, -2, -3, -4, -5 and -7 have been described in human endometrial epithelial cells. Immunohistochemical staining revealed a localization of the claudins apically in the glandular epithelial cells while weak or no staining has been described in luminal epithelial cells [33,35,36,37]. In contrast, no staining for claudins was found in the endometrial stromal cells.…”

“…In contrast, the group of Sobel described a significant upregulation only of claudin-4 transcripts and an increase in claudin-1 and -5 protein in the secretory phase [35]. In contrast to that, other groups did not observe any regulation of claudin-3 and -4 throughout the menstrual cycle [33,37,39]. Interestingly, in women undergoing IVF treatment, the absence of claudin-4 in the presence of leukemia inhibitory factor (LIF) in the endometrium could be correlated with a 6-fold higher probability of successful establishment of pregnancy compared to samples that exhibited a strong claudin-4 and a weak LIF expression [40].…”

“…As part of the cytoplasmatic component of the tight junctions, ZO-1 showed a distinct staining at the most apical part of the basolateral cell membrane of the endometrial epithelial as well as in endothelial cells [37]. For both proteins, JAM-1 as well as ZO-1, no change in the location or expression level could be observed throughout the different phases of the menstrual cycle [37,41,42]. …”

The bicellular tensile force sorts the localization of LSRs in bicellular and tricellular junctions

“…In HEE cells, adherens junction proteins were also redistributed during the different phases of the menstrual cycle. 19 Previous studies did not investigate the periodic changes in LSR localization, except using normal endometrial cells.…”