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

通过对600例不育男性、360例生育男性和320例青年男性的基因库数据进行分析，探讨了男性不育症的诊断和治疗进展。分析结果如下：1.临床研究。已发现精浆运动抑制剂与精凝素相同，精凝素是一种仅在精囊中表达的蛋白质。我们对Sg Ⅰ基因突变是否导致不育进行了研究，发现5例不育男性和8例生育男性的Sg Ⅰ基因第二外显子有180 bp的缺失，但该基因缺失与精液检查结果无相关性。我们还在其中一名有生育能力的男性中发现了Sg I缺失的产物（比正常的产物小），目前正在分析突变形式的蛋白以确定蛋白功能的差异.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、雅普和47 z/Stu三种多态性将日本男性分为四种Y单倍型，发现平均精子浓度与Y染色体类型相关。利用杆状病毒系统在昆虫细胞中表达了人Sg基因，纯化后的r-Sg蛋白具有SPMI活性.我们确定了Sg对获能的影响，获能是精子必须经历的一系列转化才能生育。Sg的作用机制之一是通过在获能诱导剂孵育过程中减少O_2来实现的.我们确定，Sg蛋白是有用的标记，精液鉴定斑点印迹免疫分析使用的Sg抗体。

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.