...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Male fetal germ cells are targets for androgens that physiologically inhibit their proliferation
【24h】

Male fetal germ cells are targets for androgens that physiologically inhibit their proliferation

机译：男性胎儿生殖细胞是生理上抑制其增殖的雄激素的靶标

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In adulthood, the action of androgens on seminiferous tubules is essential for full quantitatively normal spermatogenesis and fertility. In contrast, their role in the fetal testis, and particularly in fetal germ cell development, remains largely unknown. Using testicular feminized (Tfm) mice, we investigated the effects of a lack of functional androgen receptor (AR) on fetal germ cells, also named gonocytes. We demonstrated that endogenous andro-gens/AR physiologically control normal gonocyte proliferation. We observed an increase in the number of gonocytes at 17.5 days postconception resulting from an increase in proliferative activity in Tfm mice. In a reciprocal manner, gonocyte proliferation is decreased by the addition of DHT in fetal testis organotypic culture. Furthermore, the AR coregulator Hsp90α (mRNA and protein) specifically expressed in gonocytes was down-regulated in Tfm mice at 15.5 days postconception. To investigate whether these effects could result from direct action of androgens on gonocytes, we collected pure gonocyte preparations and detected AR transcripts therein. We used an original model harboring a reporter gene that specifically reflects AR activity by androgens and clearly demonstrated the presence of a functional AR protein in fetal germ cells. These data provide in vivo and in vitro evidence of a new control of endogenous androgens on gonocytes identified as direct target cells for androgens. Finally, our results focus on a new pathway in the fetal testis during the embryonic period, which is the most sensitive to antiandrogenic endocrine disruptors.
机译：在成年期，雄激素对生精小管的作用对于完全定量地正常生精和受精至关重要。相比之下，它们在胎儿睾丸中的作用，特别是在胎儿生殖细胞发育中的作用，仍然是未知的。使用睾丸女性化（Tfm）小鼠，我们调查了功能性雄激素受体（AR）缺乏对胎儿生殖细胞（也称为生殖细胞）的影响。我们证明了内源性雄激素/ AR生理控制正常的性腺细胞增殖。我们观察到受精后Tfm小鼠增殖活性增加导致受精后17.5天的性腺细胞数量增加。以相反的方式，通过在胎儿睾丸器官型培养物中添加DHT来减少性腺细胞增殖。此外，在受精后15.5天，Tfm小鼠的角质形成细胞中特异性表达的AR共调节因子Hsp90α（mRNA和蛋白质）被下调。为了研究这些作用是否可能是由于雄激素对角质细胞的直接作用所致，我们收集了纯净的角质细胞制剂并在其中检测到了AR转录本。我们使用的原始模型带有一个记者基因，该基因专门反映雄激素的AR活性，并清楚地证明了胎儿生殖细胞中功能性AR蛋白的存在。这些数据提供了体内和体外证据，证明了对被确定为雄激素直接靶细胞的细胞中内源雄激素的新控制。最后，我们的结果侧重于胚胎期胎儿睾丸的新途径，该途径对抗雄激素内分泌干扰物最敏感。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号