Laboratory of Clinical Immunology, National Medical Research Center for Obstetrics, Gynecology, and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, Oparina str. 4, Moscow, Russian Federation, 117997.
R&D Department, National Medical Research Center for Obstetrics, Gynecology, and Perinatology of Ministry of Healthcare of Russian Federation, Oparina str. 4, Moscow, 117997, Russia.
Reprod Biol Endocrinol. 2021 May 15;19(1):73. doi: 10.1186/s12958-021-00750-z.
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.
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-Le and MECA-79 monoclonal antibodies (MAbs).
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 Le 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.
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.
低子宫内膜容受性是影响辅助生殖技术(ART)中成功着床的主要因素之一。薄子宫内膜的不孕患者的累积临床妊娠率明显低于正常子宫内膜患者。薄子宫内膜容受性低的分子病理生理学仍研究不足。我们研究了不孕妇女薄子宫内膜腔上皮和腺上皮细胞顶表面糖萼的组成。
纳入 32 例接受体外受精(IVF)的输卵管-腹膜不孕患者。在自然月经周期中获取子宫内膜样本。患者分为两组:正常子宫内膜(≥8mm)和薄子宫内膜(<8mm)。使用 6 种生物素化凝集素(UEA-I、MAL-II、SNA、VVL、ECL、Con A)和抗-Le 和 MECA-79 单克隆抗体(MAb)对石蜡包埋的子宫内膜样本进行组织化学和免疫组织化学分析。
考虑到糖结合 MAb 的调整特异性,复杂聚糖分析显示,薄子宫内膜腔上皮细胞顶表面的 MECA-79 聚糖表达减少了 1.3 倍;这种缺陷可能会对植入产生不利影响,因为 MECA-79 聚糖是 L-选择素的配体,介导细胞间相互作用。在薄子宫内膜中发现了含有 2 型单元 Galβ1-4GlcNAcβ(LacNAc)但缺乏 GlcNAcβ 6-OH 上的磺酸基的聚糖,并且与 MECA-79 MAb 结合;它们可以被认为是子宫内膜接受性的潜在标志物。腔上皮和腺上皮细胞顶表面的凝集素染色聚糖的表达无明显差异。在薄子宫内膜和复发性着床失败的患者中,发现腔上皮和腺上皮细胞顶表面双岩藻糖基化寡糖 Le 的表达存在相关性。富含甘露糖的聚糖也表现出类似的关系。
薄子宫内膜上皮细胞区关键聚糖表达的特定特征对于子宫内膜功能层的形态发生可能至关重要,并解释了其低接受性。