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Toxic mechanisms of endocrine disrupting chemicals for reproductiue function.

内分泌干扰化学物质对生殖功能的毒性机制。

基本信息

批准号：
11839024
负责人：
SUEOKA Kou
金额：
$ 2.62万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11839024/
关键词：
c-kit spermatogonia W +W^v maturation arrest RT-PCR immunohistochemistry 免疫組織化学 +免疫組識化学 W^v mouse

项目摘要

The protooncogene of Tyrosin Kinase receptor c-kit was focused in the role of spermatogenic differentiation in testis. The implication of c-kit was examined on the aspect of gene expression and c-kit production at testicular germ cell by RT-PCR and immunohistochemistry. Hetero and homo mutant mice with two types of c-kit mutations were used for the experiments, which were W with 78 amino acids deletion and W^v with a point mutation at 790 amino acid sequence from N-terminal. Hetero mutant of W/+ and W^v/+, homo mutant of W/W^v were compared to wild type (+/+). Although c-kit m-RNA were expressed strongly at both hetero mutant and wild type, W/W^v testis expressed mutated gene. Anti-c-kit monoclonal antibody CD117 was used for immunohistochemical study. Whereas c-kit were expressed in Leidig cell of hetero and homo mutants, it was detected in spermatogonia of wild type and hetro mutants. In the protocol of present studies, testicular disfunction following exposure of toxic chemicals are determining at the mechanisms prouoked by c-kit and its gene experssion. These results suggested that c-kit had strongly implicated to the spermatogenesis especially at the differentiation of spermatogonia. This pathological status occured by the exposure of endocrine disrupting chemicals may affect the mechanisms of maturation arrest in male reproductive function.

酪氨酸激酶受体c-kit原癌基因在睾丸生精分化中的作用是研究的热点。采用RT-PCR和免疫组化方法从睾丸生殖细胞基因表达和c-kit产生方面探讨c-kit的意义。使用具有两种类型的c-kit突变的hepatitis和homo突变小鼠用于实验，所述突变是具有78个氨基酸缺失的W和具有从N-末端开始的790个氨基酸序列处的点突变的W^v。将W/+和W^v/+的hepatocellular突变体、W/W^v的homo突变体与野生型（+/+）进行比较。尽管c-kit mRNA在异源突变体和野生型中均强烈表达，但W/W^v睾丸表达突变基因。免疫组化采用抗c-kit单克隆抗体CD 117。而c-kit在异型和同型突变体的Leidig细胞中表达，在野生型和异型突变体的精原细胞中检测到。在目前的研究方案中，毒性化学品暴露后睾丸功能障碍是由c-kit及其基因表达所引起的机制决定的。这些结果提示c-kit与精子发生密切相关，尤其是在精原细胞分化阶段。这种由内分泌干扰物引起的病理状态可能影响雄性生殖功能成熟阻滞的机制。