Toxic mechanisms of endocrine disrupting chemicals for reproductiue function.

原癌基因酪氨酸激酶受体c-kit在睾丸生精分化中的作用已成为研究热点。用RT-PCR和免疫组织化学方法检测c-kit在睾丸生殖细胞基因表达和c-kit产生方面的意义。本实验选用c-kit基因缺失78个氨基酸的W和N-末端790个氨基酸的点突变W和同种突变的异种和同种突变小鼠。将W/+和W^v/+的异源突变体、W/W^v的同源突变体与野生型(+/+)进行比较。虽然c-kit m-RNA在异源突变体和野生型中都有较强的表达，但W/W^v睾丸表达突变基因。采用抗c-kit单抗CD117进行免疫组织化学研究。C-kit在异源突变株和同源突变株的精原细胞中表达，而在野生型和杂合突变株的精原细胞中表达。在目前的研究方案中，暴露于有毒化学物质后的睾丸功能障碍是由c-kit及其基因表达所引起的机制决定的。这些结果表明，c-kit与精子发生密切相关，尤其是在精原细胞的分化过程中。这种由内分泌干扰物暴露引起的病理状态可能影响男性生殖功能成熟停滞的机制。

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.