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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

为了了解内分泌干扰物对精子发生的雌激素效应，本文分析了内源性雌激素雌二醇（E2）对精子发生的作用。在精子发生的整个过程中，血清中均存在E2，睾丸中也有E2受体的表达。精原干细胞更新诱导E2植入，但被他莫昔芬（雌激素拮抗剂）抑制。在体外，E2还刺激培养的睾丸组织中的精原干细胞分裂，证实了体内观察结果。为了直接确定精原干细胞更新的调控基因，我们采用表达筛选的方法，对睾丸中受（E2）调控的基因进行了筛选。我们发现了一个先前未鉴定的cDNA克隆，其被E2刺激上调，并将其命名为eSRS 34 cDNA。eSRS 34的功能使用在 ...更多信息体外系统空泡病毒系统产生的重组eSRS 34在睾丸器官培养中诱导精原细胞有丝分裂。在雌激素性内分泌干扰物中，研究了己烯雌酚（DES）、对壬基酚（NP）和双酚A（双酚A）对小鼠睾丸器官体外培养系统精子发生的影响。单独使用这些化学物质的治疗以与E2治疗相同的方式刺激精原干细胞更新。此外，在硬骨鱼主要雄激素11-酮睾酮（11-KT）存在下，三种化合物均不影响精子发生，但DES或NP处理后，支持细胞显著增大，其结构与吞噬细胞相似。由于支持细胞的形态改变，生殖细胞数量减少。这些结果表明，DES和NP通过抑制雄激素水平影响精子发生。少