Function of Epididymis in the Recognition and Elimination of Non-viable Spermatozoa

尽管附睾环境积极促进精子存活，但精子的存在 在该地区的许多物种中都观察到了不能存活的精子群体。 退化的精子释放酶或抗原，这些酶或抗原可能对 对邻近细胞活力的影响。它可能是自身抗原的来源之一 如果它们能够逃脱血液附睾屏障，就可以诱导免疫反应。 抗精子抗体在男性中并不少见；它们的形成原因并不少见 理解，而且它们是难以纠正的不孕不育的根源。什么是 可以防止这些负面影响的附睾保护策略 男性生育能力？我们鉴定了一个64 kDa的仓鼠附睾分泌蛋白(最初 称为HEF64)，其组装成260和280 kDa的二硫键连接的低聚物。 HEF64由附睾尾部的主细胞分泌，并与 然后聚合成一层有缺陷的蛋白质“死亡茧”涂层 精子和精子碎片。260/280 kDa低聚物被称为eFGL(for 附睾纤维蛋白原样寡聚体)。生化研究表明，eFGL是 由两个亚基组成；鉴定为纤维蛋白原样蛋白-2的64 kDa多肽 33 kDa多肽，鉴定为纤维蛋白原样蛋白-1。我们的形态 研究表明，eFGL被聚合成蚕茧状的复合体， 有缺陷的管腔精子和精子碎片，而不是存活的精子群。 这项研究项目将确定这种分泌蛋白(EFGL)的生化基础。 缺陷精子的识别及其生物学效应。我们的假设是 EFGL代表了一种新颖而独特的机制来保护可存活的精子 包含退化精子的群体和/或附睾上皮 在小管腔内。拟议研究的完成将提供新的见解 探讨这种潜在独特的附睾蛋白在精子中发挥作用的机制 识别和消除有缺陷的精子。直接演示 附睾蛋白的功能似乎对制定帮助 不育男性具有正常的精子产量，但射精液的“精子质量”较低。 本项目的目标是：1.确定哪些细胞器和潜在的配体 有缺陷的精子结合附睾eFGL 2。为了确定eFGL是否与 特定的精子配体促进精子死亡和/或死亡茧聚合。

Even though the epididymal environment actively promotes sperm survival, the presence of the nonviable sperm population in this region has been observed in many species. Degenerating spermatozoa release enzymes or antigens that could have a detrimental effect on the viability of the neighboring cells. It may be a source of autoantigens that could induce the immune response if they can escape from the blood-epididymis barrier. Anti-sperm antibodies are not uncommon in men; they develop for reasons that are not understood, and they are a source of infertility that is difficult to correct. What are the protective strategies of the epididymis that could prevent these negative impacts on male fertility? We identified a hamster epididymal secretory protein of 64kDa (originally termed HEF64) which assembles into 260 and 280kDa disulfide-linked oligomers. HEF64 is secreted by principal cells of the cauda epididymidis and specifically binds to and then polymerizes into a proteinaceous “death cocoon” coating defective spermatozoa and sperm fragments. The 260/280 kDa oligomers are termed eFGL (for epididymal fibrinogen-like oligomer). Biochemical studies revealed that eFGL is composed of two subunits; the 64kDa polypeptide identified as fibrinogen-like protein-2 and the 33kDa polypeptide identified as fibrinogen-like protein-1. Our morphological studies demonstrated that the eFGL is polymerized into a cocoon-like complex, masking defective luminal spermatozoa and sperm fragments, not the viable sperm population. This research project will define the biochemical basis of this secretory protein (eFGL) recognition and its biological effects on the defective spermatozoa. Our hypothesis is that eFGL represents a novel and unique mechanism to shield the viable sperm population and/or the epididymal epithelium from degenerating spermatozoa contained within the tubule lumen. Completion of the proposed studies will provide new insights into the mechanisms by which the potentially unique epididymal protein functions in the recognition and elimination of defective spermatozoa. Direct demonstration of epididymal protein function would seem critical for development of strategies to help infertile males with normal sperm production but low “sperm quality” of the ejaculate. The aims of this project are: 1. To identify which organelles and potential ligands of defective spermatozoa bind the epididymal eFGL 2. To determine if eFGL binding to specific sperm ligands promotes sperm death and/or death cocoon polymerization.