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上皮钙黏蛋白在人类男性生殖道和配子中的表达及其参与受精的证据。

Expression of epithelial cadherin in the human male reproductive tract and gametes and evidence of its participation in fertilization.

作者信息

Marín-Briggiler C I, Veiga M F, Matos M L, Echeverría M F González, Furlong L I, Vazquez-Levin M H

机构信息

Instituto de Biología y Medicina Experimental, National Research Council of Argentina (CONICET), University of Buenos Aires, Vuelta de Obligado 2490, Buenos Aires, Argentina.

出版信息

Mol Hum Reprod. 2008 Oct;14(10):561-71. doi: 10.1093/molehr/gan053. Epub 2008 Oct 1.

Abstract

Epithelial cadherin (E-cadherin) has been involved in several calcium-dependent cell-cell adhesion events; however, its participation in gamete interaction has not been fully investigated. Our results have demonstrated expression of E-cadherin mRNA in the human male reproductive tract showing higher levels in the caput, corpus and cauda epididymis than in the testis. The mature 122 kDa E-cadherin was detected in epididymal protein extracts and was localized in the epithelial cells from the three epididymal regions. Moreover, the 86 kDa E-cadherin ectodomain was found in cauda epididymal and seminal plasma. Western immunoblotting of human sperm protein extracts allowed the identification of four E-cadherin forms (122, 105, 97 and 86 kDa). The protein was localized in the acrosomal region of intact spermatozoa, remained associated with the head of acrosome-reacted cells and was also detected on the oocyte surface. A similar localization was determined for other proteins of the adhesion complex (beta-catenin and actin). Spermatozoa incubated with anti-E-cadherin antibodies showed impaired binding to homologous zona pellucida (ZP); in addition, presence of these antibodies inhibited the penetration of human spermatozoa to ZP-free hamster oocytes. The results presented here describe the expression of E-cadherin in the male reproductive tract and gametes and strongly suggest its involvement in adhesion events during human fertilization. The identification of proteins involved in gamete interaction will contribute to the understanding of the molecular basis of fertilization and help in the diagnosis and treatment of infertility.

摘要

上皮钙黏蛋白(E-钙黏蛋白)参与了多种钙依赖性细胞间黏附事件;然而,其在配子相互作用中的作用尚未得到充分研究。我们的结果表明,E-钙黏蛋白mRNA在人类男性生殖道中表达,在附睾头、附睾体和附睾尾中的水平高于睾丸。在附睾蛋白提取物中检测到成熟的122 kDa E-钙黏蛋白,并定位于三个附睾区域的上皮细胞中。此外,在附睾尾和精浆中发现了86 kDa的E-钙黏蛋白胞外域。对人类精子蛋白提取物进行的Western免疫印迹鉴定出四种E-钙黏蛋白形式(122、105、97和86 kDa)。该蛋白定位于完整精子的顶体区域,在顶体反应细胞的头部仍有结合,并在卵母细胞表面也有检测到。对黏附复合体的其他蛋白(β-连环蛋白和肌动蛋白)也确定了类似的定位。用抗E-钙黏蛋白抗体孵育的精子与同源透明带(ZP)的结合受损;此外,这些抗体的存在抑制了人类精子穿透无ZP的仓鼠卵母细胞。本文给出的结果描述了E-钙黏蛋白在男性生殖道和配子中的表达,并强烈表明其参与了人类受精过程中的黏附事件。鉴定参与配子相互作用的蛋白质将有助于理解受精的分子基础,并有助于不孕症的诊断和治疗。

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