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Development of diagnosis and therapy for male infertility ; Clinical genetic research including the analysis of the infertility-related gene

男性不育症诊断和治疗的发展；

基本信息

批准号：
10557145
负责人：
IWAMOTO Teruaki
金额：
$ 8.19万
依托单位：
St.Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

We investigated the development of diagnosis and therapy for male infertility by analyzing data from a previously constructed gene bank including 600 infertile men, 360 fertile men and 320 young men. The results of the analysis are as follows :Clinical research ; 1. Seminal plasma motility inhibitor has been found to be identical to Semenogelin I)Sg), a protein expressed exclusively in the seminal vesicles. We investigated whether the mutation of Sg I causes infertility, and found a deletion of 180 bp in the second exon of the Sg I in 5 infertile men and 8 fertile men, but there was no correlation between the deletion of this gene and seminal findings. We also found the smaller products of deleted Sg I(than normal one) in one of these fertile men, and the mutant form protein is currently being analyzed to determine the difference in protein function.2. We have hypothesized that Y chromosomes from different male lineages have different structures and different constituent genes involved in spermatogenesis. Nakahori's group classified Japanese males into four Y haplotypes according to three polymorphisms, SRY, YAP and 47z/Stu, and found that the mean sperm concentration correlates with the Y chromosome type.Basic Research 1. We expressed human Sg genes in insect cells using a baculovirus system, and found that the purified r-Sg proteins showed SPMI activity by themselves.2. We determined the effect of Sg on capacitation, which is the series of transformations that spermatozoa must undergo to become fertile. One mechanism of Sg action occurs via the reduction of O_2 during incubation with capacitation inducer.3. We determined that Sg protein is useful as a marker for semen identification by dot-blot-immunoassay using the Sg antibodies.

通过分析先前构建的包括600名不育男性、360名可育男性和320名年轻男性的基因库数据，研究了男性不育症的诊断和治疗进展。分析结果如下：临床研究；1. 精浆运动抑制剂已被发现与精囊蛋白（Semenogelin）相同，后者是一种仅在精囊中表达的蛋白质。我们研究了Sg I突变是否导致不育，在5名不育男性和8名可育男性中发现Sg I第二外显子缺失180bp，但该基因的缺失与精液结果没有相关性。我们还在其中一名有生育能力的男性中发现了较小的Sg I缺失产物（比正常产物），目前正在分析突变形式的蛋白质，以确定蛋白质功能的差异。我们假设来自不同男性谱系的Y染色体具有不同的结构和参与精子发生的不同组成基因。Nakahori的研究小组根据SRY、YAP和47z/Stu三种多态性将日本男性分为四种Y单倍型，并发现平均精子浓度与Y染色体类型相关。基础研究我们利用杆状病毒系统在昆虫细胞中表达了人Sg基因，发现纯化后的r-Sg蛋白本身具有SPMI活性。我们确定了Sg对获能性的影响，这是精子必须经历的一系列转化才能成为可育的。Sg作用的一种机制是通过在容化诱导剂的培养过程中O_2的还原发生的。我们确定Sg蛋白可以作为精液鉴定的标记物，使用Sg抗体进行点印迹免疫分析。