Systematic analyses of murine masculinization processes based on genital sex differentiation parameters
Systematic analyses of murine masculinization processes based on genital sex differentiation parameters
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基于生殖器性别分化参数的小鼠雄性化过程的系统分析
DOI：
10.1111/dgd.12247
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Yamada G
中科院分区：
文献类型：
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作者：
Suzuki H;Suzuki K;Yamada G
小鼠外生殖器和会阴的生殖组织在雄性和雌性中具有显著不同的特征。尽管对小鼠外生殖器和会阴的发育进行了大量的研究，但评价外生殖器和会阴发育性差异的参数仍然有限。此外，阐明外生殖器和会阴的最新发育信号需要生殖科学中基因功能的最新知识。为了促进生殖器官形成的研究，建立雄激素介导的外生殖器和会阴形成的参数是必要的。在这项研究中，我们提出了生殖器性别分化参数（GSDP），这是一组基于系统三维组织重建和累积组织学分析的发育参数。我们通过分析小鼠模型、雄激素抑制剂诱导的雌性化实验和Mafb突变型尿道分化缺陷小鼠，用GSDP定义了外生殖器和会阴的性别差异。尿道参数显示雄激素抑制剂（芬那肽）治疗显著降低。然而，生殖器结节（GT）的大小参数不受这种治疗。这些结果表明，胚胎GT大小和尿道形成对双氢睾酮的敏感性不同。此外，我们还通过GSDP评估了Mafb突变小鼠尿道缺陷的程度。因此，GSDP是一组有用的参数来定义外生殖器和会阴发育过程中的性别差异。
Murine reproductive tissues of the external genitalia and perineum develop with remarkably distinctive characteristics in males and females. Although many researches on such mouse organ development have been reported, there are still limited parameters that evaluate the developmental sexual differences of external genitalia and perineum. Furthermore, elucidation of the recent developmental signals for the external genitalia and perineum requires up‐to‐date knowledge of gene functions in reproductive science. To promote researches on reproductive organ formation, establishment of parameters for the androgen‐mediated formation of external genitalia and perineum is essential. In this study, we propose genital sex differentiation parameters (GSDP), a set of developmental parameters based on systematic three‐dimensional tissue reconstruction and cumulative histological analyses. We define the sexual differences of external genitalia and perineum by GSDP through analyzing mouse models, androgen inhibitor‐induced feminization experiments andMafbmutant mouse with defective urethral differentiation. The urethral parameters displayed prominent reduction by the androgen inhibitor (finasteride) treatment. However, genital tubercle (GT) size parameters were not affected by such treatment. These results indicated that sensitivity to dihydrotestosterone was different between embryonic GT size and urethral formation. Furthermore, we evaluated the extent of urethral defects ofMafbmutant mice by GSDP. Thus, GSDP is a set of useful parameters to define the sexual differences during external genitalia and perineum development.