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Abstract：
BACKGROUND: Low 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.
METHODS: Thirty-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).
RESULTS: Complex 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.
CONCLUSIONS: 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.
METHODS: Thirty-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).
RESULTS: Complex 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.
CONCLUSIONS: 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.
摘要：
背景：低子宫内膜容受性是影响辅助生殖技术（ART）成功植入的主要因素之一。子宫内膜薄型不孕患者的累积临床妊娠率明显低于子宫内膜正常患者。薄子宫内膜低接受性的分子病理生理学仍未得到充分研究。我们已经研究了不育妇女的薄子宫内膜中管腔和腺上皮细胞顶表面的糖萼的组成。
方法：本研究纳入了32例接受体外受精（IVF）的输卵管腹膜不孕症患者。在自然月经周期中获得子宫内膜样品。患者分为两组：子宫内膜正常（≥8mm）和子宫内膜薄（<8mm）。使用六种生物素化的凝集素（UEA-I，MAL-II,SNA,VVL,ECL,ConA）和抗LeY和MECA-79单克隆抗体（MAb）。
结果：考虑到聚糖结合单克隆抗体的调节特异性的复合聚糖分析显示，与正常子宫内膜相比，薄子宫内膜的管腔上皮细胞顶表面上MECA-79聚糖的表达减少了1.3倍；这种缺乏可能对植入产生不利影响，因为MECA-79聚糖是L-选择素的配体并介导细胞间相互作用。含有2型单位Galβ1-4GlcNAcβ（LacNAc）但在GlcNAcβ的6-OH上缺乏磺基残基的聚糖，并与MECA-79MAb结合;它们可以被认为是子宫内膜容受性的潜在标志物。凝集素染色的聚糖在腔和腺上皮细胞的顶表面上的表达没有显着差异。在子宫内膜薄型和复发性种植失败的患者中，发现二岩藻糖基化寡糖LeY在腔和腺上皮细胞顶表面的表达之间存在相关性。对于富含甘露糖的聚糖显示了类似的关系。
结论：薄型子宫内膜上皮区室中关键聚糖表达的特定特征可能对子宫内膜功能层的形态发生至关重要，并解释了其低接受性。
方法：本研究纳入了32例接受体外受精（IVF）的输卵管腹膜不孕症患者。在自然月经周期中获得子宫内膜样品。患者分为两组：子宫内膜正常（≥8mm）和子宫内膜薄（<8mm）。使用六种生物素化的凝集素（UEA-I，MAL-II,SNA,VVL,ECL,ConA）和抗LeY和MECA-79单克隆抗体（MAb）。
结果：考虑到聚糖结合单克隆抗体的调节特异性的复合聚糖分析显示，与正常子宫内膜相比，薄子宫内膜的管腔上皮细胞顶表面上MECA-79聚糖的表达减少了1.3倍；这种缺乏可能对植入产生不利影响，因为MECA-79聚糖是L-选择素的配体并介导细胞间相互作用。含有2型单位Galβ1-4GlcNAcβ（LacNAc）但在GlcNAcβ的6-OH上缺乏磺基残基的聚糖，并与MECA-79MAb结合;它们可以被认为是子宫内膜容受性的潜在标志物。凝集素染色的聚糖在腔和腺上皮细胞的顶表面上的表达没有显着差异。在子宫内膜薄型和复发性种植失败的患者中，发现二岩藻糖基化寡糖LeY在腔和腺上皮细胞顶表面的表达之间存在相关性。对于富含甘露糖的聚糖显示了类似的关系。
结论：薄型子宫内膜上皮区室中关键聚糖表达的特定特征可能对子宫内膜功能层的形态发生至关重要，并解释了其低接受性。
