MUC1 and endometrial receptivity

Abstract

Mucins, best known as the major constituent of mucus, are a family of highly glycosylated, high molecular weight (> or = 200 kDa) glycoproteins present on the surface of human epithelial cells. MUC1 has the features of an integral membrane protein. It has an extracellular tandem repeat domain that forms the major part of the core protein, and results in a highly repetitive structure, which is extremely immunogenic. In the protein there is also a proteolytic cleavage site reported in the proximal extracellular domain. The secreted form of MUC1 lacks the cytoplasmic tail, but it is not clear whether this results from alternative splicing or proteolysis and release of the free extracellular domain. The locus of the MUC1 gene is on band 21 of the long arm of chromosome 1 (1q21). Anti-adhesion properties of this mucin are probably the result of the unique structure of the molecule. In mouse uterine epithelium, the homologue MUC1 is regulated with reduced expression in the implantation period, but in humans, expression is high during the peri-implantation period. MUC1 may inhibit the interaction between trophoblast and apical epithelium adhesion molecules at the time of implantation, giving the possibility of forming a uterine barrier for implantation.

Interaction of extravillous trophoblast galectin-1 and mucin(s)—Is there a functional relevance?

“…24 Much evidence clearly points to hormonal regulation of MUC1 expression in the endometrium, with cyclically regulated expression of core protein and glycan sialylation, where maximum levels occur in the secretory phase of the menstrual cycle. 25 Specific MUC1 structures and the abundance of sialic acid and sulfate residues may subsequently inhibit interaction between the embryo and maternal apical adhesion molecules during implantation. Thus, the high density of MUC1 molecules must be lost from the implantation site if embryo implantation is to occur.…”

Steroid hormone regulation of Clca3 expression in the murine uterus

“…In this model, antisense Clca3 therapy effectively suppressed the asthma phenotype, whereas Clca3 overexpression exacerbated the condition (Nakanishi et al 2001). Changes in MUC1 glycoform expression have been related to a phase of the menstrual cycle and endometrial receptivity in a number of studies (Meseguer et al 1998, Lagow et al 1999, Aplin et al 2001. Failure of embryo implantation was associated with an abnormal endometrial expression of MUC1 mucin and retention of PGR, particularly in epithelial cells (Horne et al 2005).…”

Molecular mechanisms of membrane interaction at implantation

“…The absence of such mucins from the basolateral cell surface in normal luminal endometrial epithelium defines these cells as showing a primary polarity and an apical barrier. The anti-cellular adhesion molecule mucin 1 (MUC1), an integral membrane glycoprotein expressed on the apical surface of secretory epithelial cells, is a major component of interest in the glycocalyx (Meseguer et al, 1998;Aplin et al, 2001). MUC1 is capable of sterically hindering interactions with other cell surfaces that are mediated by adhesion molecules with smaller conformations, due to its high expression, density of glycosylation, and extended conformation (Hilkens et al, 1992).…”

“…In mice and rabbits, MUC1 levels are reduced during implantation (Aplin and Hey, 1995;Surveyor et al, 1995;Hoffman et al, 1998;Meseguer et al, 1998Meseguer et al, , 2001Dharmaraj et al, 2010). Conversely, in humans, MUC1 levels increase during the midsecretory phase and peak 7 days after the luteal hormone (LH) surge to coincide with embryo implantation (Meseguer et al, 1998).…”

“…In mice and rabbits, MUC1 levels are reduced during implantation (Aplin and Hey, 1995;Surveyor et al, 1995;Hoffman et al, 1998;Meseguer et al, 1998Meseguer et al, , 2001Dharmaraj et al, 2010). Conversely, in humans, MUC1 levels increase during the midsecretory phase and peak 7 days after the luteal hormone (LH) surge to coincide with embryo implantation (Meseguer et al, 1998). Multiple studies have reported that patients suffering from recurrent implantation failure have significantly lower levels of MUC1 in the endometrium during the window of implantation, compared to healthy fertile women Xu et al, 2012;Bastu et al, 2015).…”