Molecular mechanisms of the influences of endocrine disruptors on spermatogenesis using Japanese eel.

内分泌干扰物对日本鳗鱼精子发生影响的分子机制。

基本信息

批准号：
11839001
负责人：
MIURA Takeshi
金额：
$ 2.3万
依托单位：
HOKKAIDO 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 2001
项目状态：
已结题

项目摘要

In order to understand the estrogenic influence of endocrine disruptors on spermatogenesis, I analyzed the function of endogenous estrogen : estradiol-17β (E2) on spermatogenesis. E2 was present in the serum and its receptor was expressed in the testis during the whole process of spermatogenesis. Spermatogonial stem cell renewal was induced by E2 implantation but was suppressed by tamoxifen (antagonist of estrogen). In vitro, E2 also stimulates spermatogonial stem cell division in cultured testicular tissue, confirming the in vivo observations. These resuits clearly show that estrogen is an indispensable "male hormone" in early spermatogenetic cycle.To determine the genes regulated spermatogonial stem cell renewal directly, we have applied an expression screening to identify genes whose expression is regulated by (E2) in testes. We found one previously unidentified cDNA clone that was up-regulated by E2 stimulation, and named it eSRS34 cDNA. The function of eSRS34 was examined using in … More vitro systems. Recombinant eSRS34 produced by vaculovirus system induced spermatogonial mitosis in testicular organculture. We conclude that eSRS34 is "spermatogonial stem cell renewal factor".Among the estrogenic endocrine disruptors, the influences of diethylstilbestrol (DES), para-nonylphenol (NP) and bis-phenol A on spermatogenesis was examined in vitro testicular organ culture system. The treatments with these chemicals alone stimulates spermatogonial stem cell renewal in the same manner of E2 treatment. In addition, under the existence of 11-ketotestosterone (11-KT), the major androgen in teleosts, these three chemicals did not disturb the progress of spermatogenesis, but the treatment of DES or NP stimulated the remarkable enlargement of Sertoli cell, its structure was similar that of the phagocytotic cells. As a result of the morphological changes of Sertoli cells, the number of germ cells was decreased. These results indicate that DES and NP affected the spermatogenesis by the existenee of the androgen. Less

为了理解精子发生的散言，我分析了内源性的：L-17β（E2）对精子发生的作用。通过E2植入，但在培养的睾丸组织中被他莫昔芬（雌激素的拮抗剂）抑制。常规的精子干细胞更新直接撒谎，以识别其表达在睾丸中受（E2）调节的基因。 ...更多的体外系统。单独使用Thesh化学物质的治疗可刺激精子图以相同的E2处理方式刺激干细胞的更新。这些结果降低了生殖细胞的塞托利细胞。