Abstract
BackgroundLow endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women.MethodsThirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-LeY and MECA-79 monoclonal antibodies (MAbs).ResultsComplex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity.Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide LeY on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans.ConclusionsSpecific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity.
Highlights
Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART)
Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity
We found no significant intergroup differences in the expression of both terminal and subterminal residues of N-acetyllactosamine, as well as of fucosylated glycans stained with Ulex europaeus agglutinin-I (UEA-I); similar correlations of the expression of the corresponding glycoconjugates in the studied epithelial compartments of thin and normal endometrium apparently reflect the universal patterns of expression of glycans’ functional residues, common for glycoconjugates of the endometrial glycocalyx, and may feature appropriate changes during the middle secretory phase, which do not affect endometrial receptivity
Summary
Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Molecular pathophysiology of low receptivity of thin endometrium remains understudied. A predictive value of this indicator is contradictory, since pregnancies have been reported to occur in patients with endometrium 4–5 mm, suggesting that receptivity might be not necessarily related to endometrial thickness [5, 6]. Many experts agree that insufficient endometrial thickness may reduce the cumulative clinical pregnancy rate, live birth rate [7], and be associated with small for gestational age neonates and obstetric complications caused by poor placentation [8]. A complex assessment of the molecular composition of the main functional structures of endometrium in a natural cycle is needed. This could allow prediction of the endometrium potential for blastocyst acceptance and trophoblast invasion. Molecular research should be obviously focused on the key molecules involved in intercellular interactions mediating these processes
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