DeLoia J A, Krasnow J S, Brekosky J, Babaknia A, Julian J, Carson D D
Department of Cell Biology and Physiology, University of Pittsburgh, PA 15213, USA.
Hum Reprod. 1998 Oct;13(1O):2902-9. doi: 10.1093/humrep/13.10.2902.
The cell membrane-associated, polymorphic mucin, MUC1, has been proposed to hinder implantation by virtue of its anti-adhesive properties. Consistent with this proposal is the observation of a dramatic decrease in MUC1 protein and mRNA expression in the uterine epithelium of several species at the time of implantation. In contrast, little change in glandular epithelial expression of MUC1 protein or its mRNA during the peri-implantation period has been detected in humans. However, expression in the luminal epithelium, i.e. the epithelium involved in embryo attachment, has not been reported. Using tissue samples with a clearly defined luminal epithelium and antibodies directed against the cytoplasmic domain found in all cell-associated MUC1 species (CT-1) and against two MUC1 ectodomain epitopes, HMFG-1 and HMFG-2, we demonstrate that MUC1 expression in the luminal epithelium is maintained throughout the menstrual cycle. The staining observed with CT-1 correlates with that seen with HMFG-2, but not HMFG-1. HMFG-1 reactivity was high in all regions except basal glands in the mid proliferative endometrium and fell to very low levels throughout the tissue in the mid secretory phase. In all cases, HMFG-1 reactivity could be restored by predigestion with keratanase or neuraminidase which removes keratan sulphates and sialic acids, respectively. These observations suggest that regionally restricted glycosylation generates an altered external structure of MUC1. These alterations appear to decrease accessibility to the MUC1 protein core region and are maximal in luminal epithelium at the receptive phase. Due to their large highly extended structures, MUC1 ectodomains are very likely to be among the first cell surface components encountered during human blastocyst attachment to the luminal epithelium. Thus, MUC1 either must be locally removed during the attachment process or functions actually to promote the initial steps in embryo adhesion to the apical surface of the human uterine epithelium.
细胞膜相关的多态性粘蛋白MUC1，因其抗粘附特性而被认为会阻碍着床。与这一观点相符的是，在几种物种着床时，子宫上皮中MUC1蛋白和mRNA表达显著下降。相比之下，在人类着床期前后，MUC1蛋白或其mRNA在腺上皮中的表达变化不大。然而，尚未有关于其在腔上皮（即参与胚胎附着的上皮）中表达的报道。我们使用具有明确界定的腔上皮的组织样本，以及针对所有细胞相关MUC1物种中发现的胞质结构域（CT-1）和两个MUC1胞外结构域表位HMFG-1和HMFG-2的抗体，证明MUC1在腔上皮中的表达在整个月经周期中保持稳定。CT-1染色与HMFG-2染色相关，但与HMFG-1无关。在增殖中期子宫内膜中，除基底腺外，所有区域的HMFG-1反应性都很高，而在分泌中期，整个组织中的HMFG-1反应性降至非常低的水平。在所有情况下，分别用角蛋白酶或神经氨酸酶预先消化去除硫酸角质素和唾液酸后，HMFG-1反应性均可恢复。这些观察结果表明，区域限制性糖基化产生了MUC1外部结构的改变。这些改变似乎降低了对MUC1蛋白核心区域的可及性，并且在接受期的腔上皮中最为明显。由于其大的高度伸展结构，MUC1胞外结构域很可能是人类囊胚附着于腔上皮过程中首先遇到的细胞表面成分之一。因此，MUC1要么在附着过程中必须局部去除，要么实际上起到促进胚胎粘附于人类子宫上皮顶端表面初始步骤的作用。
