Unexpected roles of the male tract mesenchyme in female reproductive tract formation

项目摘要/摘要： 年，女性生殖道结构异常影响0.1%-3.0%的活产。 人类是导致成年后不孕不育问题的主要原因。因此，它是 重要的是要阐明胚胎是如何在 细胞和分子水平。从长远来看，了解细胞和分子机制 指导女性生殖道的形成将有助于我们制定更好的诊断策略， 治疗和预防妇科综合征和性发育障碍。 在早期胎儿阶段，女性胚胎同时拥有原始的男性和女性 生殖道。女性生殖道系统的适当形成需要两个 步骤：1.性分化过程中原始男性肌束的退化；保留和 原始女性束分化为输卵管、子宫和部分阴道。这个 原始的雄性和雌性原始区被它们各自的间充质所包围，这决定了 这些地区的命运和分化。这项提议的重点是雄性间质， 我发表的和初步的结果表明，它在女性中扮演着关键角色 生殖道形成。在指导阶段，我将接受下一代的培训 基于测序的方法，并将检验我的假设，即男性间质细胞起作用 通过转录因子COUP-TFII来调节雄性生殖道的消除，第一步 雌性生殖道形成。在独立阶段，我将使用下一代测序 研究第二步中雄性间充质分化的基本方法 女性生殖道的形成。我将进一步验证我的假设，即男性生殖道 间充质是女性生殖道内间充质细胞的重要来源。 在这些研究的结论中，我希望建立一个模型来阐明意想不到的角色 男性生殖道间充质细胞在女性生殖道形成中的作用。我的学习将会 为我们了解生殖道疾病提供了一个切入点 间充质分化。

Project Summary/Abstract: Abnormalities in the female reproductive tract formation affects 0.1%-3.0% of live births in humans, a main cause of infertility issues when individuals reach their adulthood. It is therefore important to elucidate how the embryo forms a functional female reproductive tract system at the cellular and molecular levels. In the long run, understanding cellular and molecular mechanisms directing the female reproductive tract formation will help us develop better strategies for diagnosis, treatement and prevention of gynecological syndromes and disorders of sexual development. At the early fetal stage, a female embryo possesses both primitive male and female reproductive tracts. The appropriate formation of the female reproductive tract system requires two steps: 1st. regression of the primitive male tract during sexual differentiation; 2nd. retention and differentiation of the primitive female tract into the oviduct, the uterus and the partial vagina. The primitive male and female tracts are surrounded by their respective mesenchyme, which determine the fate and differentiation of the tracts. The focus of this proposal is the male tract mesenchyme, which has been suggested by my published and preliminary results to play critical roles in female reproductive tract formation. During the mentored phase, I will obtain training in next generation sequencing based approaches, and will test my hypothesis that the male tract mesenchyme acts through a transcriptional factor COUP-TFII to regulate the male tract elimination, the 1st step of female reproductive tract formation. In the independent phase, I will use next generation sequencing based approaches to investigate the differentiation of the male tract mesenchyme during the 2nd step of female reproductive tract formation. I will further test my hypothesis that the male tract mesenchyme provides a critical source of mesenchymal cells in the female reproductive tract. At the conclusion of these studies, I expect to establish a model elucidating unexpected roles of the male tract mesenchyme in the formation of the female reproductive tract. My studies will provide us an entry point to understand reproductive tract diseases associated with perturbed mesenchymal differentiation.