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

基本信息

批准号：
10361538
负责人：
Fei Zhao
金额：
$ 23.78万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-24 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10361538
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&apos 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

项目摘要

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：女性生殖道的异常会影响0.1％-3.0％的活产人类是个人成年时不孕问题的主要原因。因此是重要的是要阐明胚胎如何形成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，雌性胚胎具有原始雄性和雌性生殖道。女性生殖道系统的适当形成需要两个步骤：第一。性别分化过程中原始男性的回归；第二。保留和原始雌性区域分化为输卵管，子宫和部分阴道。这原始的雄性和雌性束被各自的间充质包围，这决定了区域的命运和分化。该提议的重点是雄性间充质，我已发表的初步结果提出了这一点，以在女性中扮演关键角色生殖道的形成。在指导阶段，我将获得下一代培训基于测序的方法，并将检验我的假设，即男性道中充质起作用通过转录因子coup-tfii来调节男性消除，这是第一步女性生殖道的形成。在独立阶段，我将使用下一代测序基于第二步中研究男性裂纹间质分化的方法女性生殖道的形成。我将进一步检验我的男性道的假设间充质提供了女性生殖道中间充质细胞的关键来源。在这些研究的结论中，我希望建立一个阐明意外角色的模型雄性生殖道的形成中雄性间质的。我的学习会为我们提供一个了解与扰动相关的生殖道疾病的切入点间充质分化。