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.

项目概要/摘要： 女性生殖道发育异常影响0.1%-3.0%的活产， 人类，当个体达到成年期时不孕问题的主要原因。因此 重要的是要阐明胚胎如何形成一个功能性的女性生殖道系统， 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开发更好的诊断策略， 治疗和预防妇科综合症和性发育障碍。 在早期胎儿阶段，女性胚胎具有原始男性和女性 生殖道女性生殖道系统的适当形成需要两个 步骤：1.退化的原始男性道在性分化;第二。保留和 原始雌性生殖道分化为输卵管、子宫和部分阴道。的 原始的男性和女性管道被各自的间充质包围，这决定了 的命运和分化的大片。这项建议的重点是男性管道间充质， 我发表的初步结果表明，它在女性中起着关键作用， 生殖道形成在指导阶段，我将获得下一代培训 基于测序的方法，并将测试我的假设，即男性道间充质的行为， 通过转录因子COUP-TFII来调节雄道消除， 女性生殖道的形成在独立阶段，我将使用下一代测序 研究第二步期间雄性管道间充质分化的基础方法 女性生殖道的形成我将进一步验证我的假设， 间充质提供了雌性生殖道中间充质细胞的关键来源。 在这些研究的结论中，我希望建立一个模型，阐明意想不到的作用 男性生殖道间充质在女性生殖道形成过程中的作用。我的研究会 为我们提供了一个切入点，以了解生殖道疾病与扰动 间充质分化