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

男性生殖道间充质在女性生殖道形成中的意外作用

• 批准号: 10132364
• 负责人: Fei Zhao
• 金额: $ 24.06万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-24 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132364
• 关键词: Ablation; Adult; Affect; Androgens; Biological Process; Candidate Disease Gene; Cells; ChIP-seq; Defect; Development; Diagnosis; Disease; Embryo; Excision; Female; Future; Gene Expression; Genes; Human; Individual; Infertility; Knock-out; Lead; Life Cycle Stages; Live Birth; Mammalian Oviducts; Men' s Role; Mentors; Mesenchymal; Mesenchymal Differentiation; Mesenchyme; Modeling; Molecular; Nucleic Acid Regulatory Sequences; Organ; Phase; Play; Population; Prevention; Process; Publishing; Regulation; Reproductive Health; Role; Science; Sex Differentiation; Source; Syndrome; System; Testing; Tissues; Training; Uterus; Vagina; Woman; apoAI regulatory protein-1; base; chicken ovalbumin upstream promoter-transcription factor; differential expression; fetal; male; next generation sequencing; novel; reproductive tract; sex development disorder; single cell sequencing; spatiotemporal; transcription factor

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.

项目摘要/摘要： 女性生殖道形成异常影响 0.1%-3.0% 的活产 人类成年后不孕问题的主要原因。因此是 对于阐明胚胎如何形成功能性女性生殖道系统非常重要 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症和性发育障碍。 在胎儿早期，雌性胚胎同时具有原始的雄性和雌性 生殖道。女性生殖系统的适当形成需要两个条件 步骤： 1.性分化过程中原始雄性生殖道的退化；第二。保留和 原始女性管道分化为输卵管、子宫和部分阴道。这 原始的雄性和雌性束被各自的间质包围，这决定了 这些区域的命运和分化。该提案的重点是男性生殖道间质， 我发表的初步结果表明，这在女性中发挥着关键作用 生殖道的形成。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，即男性管道间充质发挥作用 通过转录因子COUP-TFII来调节男性肠道消除，第一步 女性生殖道的形成。在独立阶段，我会使用二代测序 基于方法来研究第二步中雄性道间充质的分化 女性生殖道的形成。我将进一步检验我的假设，即男性生殖道 间充质提供了女性生殖道间充质细胞的重要来源。 在这些研究结束时，我希望建立一个模型来阐明意想不到的角色 男性生殖道间充质在女性生殖道形成中的作用。我的学业将 为我们了解与紊乱相关的生殖道疾病提供了一个切入点 间质分化。