Life history of the menstruating uterus

经期子宫的生活史

• 批准号: 10472829
• 负责人: Kara Lavidge McKinley
• 金额: $ 151.33万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10472829
• 关键词: Address; Adenomyosis; Affect; Animal Model; Clinical; Disease; Endometrial; Endometrial Carcinoma; Endometrium; Goals; Growth and Development function; Human; Incidence; Infertility; Longevity; Mammals; Menstruation; Molecular; Mus; Natural regeneration; Organ; Pathology; Persons; Population; Pregnancy; Process; Puberty; Rattus; Regenerative Medicine; Regenerative research; Risk; Rodent; System; Testing; Time; Tissues; Uterus; Woman; Work; combat; endometriosis; fascinate; improved; innovation; insight; life history; offspring; programs; regenerative; repaired; reproductive; stem cell therapy; transgender men

PROJECT SUMMARY The uterus has the unique ability to support the growth, development, and eventual delivery of offspring. The non-pregnant uterus is no less remarkable: the uterine lining (endometrium) undergoes repeated cycles of shedding during menstruation and subsequent repair, ultimately regenerating approximately 400 times over the reproductive lifespan. This repeated, scarless regenerative process holds immense potential for the identification of new strategies to replace old or damaged tissues, which is a major goal for regenerative medicine. Moreover, understanding endometrial regeneration has important clinical implications, as excessive or insufficient endometrial regeneration gives rise to pathologies that affect the lives of hundreds of millions of women, non- binary people, and transgender men around the world. It is critical to address the longstanding unmet needs of people with endometriosis, adenomyosis, infertility, and to combat the rising incidence of endometrial cancers. The goal of this project is to identify the molecular and cellular basis for regeneration of the menstruating endometrium. A major challenge for the field is that humans belong to a very small group of mammals that menstruate. Thus, although animal models propel many scientific studies, common animal models such as mice and rats have limited utility for studies of menstruation. This project uses the common spiny mouse, which is the only known menstruating rodent, to perform functional tests of the requirements for menstruation. In parallel, we will develop approaches to determine how the human endometrium changes over time. Using these approaches, we aim to understand how the endometrium changes when menstruation begins during puberty and restarts after pregnancy. The proposed studies are an ideal fit for the New Innovator program because our understanding of the menstruating endometrium has lagged far behind more commonly studied regenerative organs. Thus, we must take strategic risks to propel us towards more precise mechanistic understanding of menstruation, a fascinating process that affects the lives of large proportions of the population.

项目摘要 子宫具有支持后代生长、发育和最终分娩的独特能力。的 非妊娠子宫同样引人注目：子宫内膜（子宫内膜）经历重复的周期， 月经期间脱落和随后的修复，最终再生约400倍， 生殖寿命这种重复的、无疤痕的再生过程具有巨大的识别潜力。 新的策略来替换旧的或受损的组织，这是再生医学的一个主要目标。此外，委员会认为， 了解子宫内膜再生具有重要的临床意义， 子宫内膜再生引起的病理影响了数亿妇女的生活， 二元人和跨性别男性。必须解决长期未得到满足的需求， 子宫内膜异位症、子宫腺肌症、不孕症患者，并与不断上升的子宫内膜癌发病率作斗争。 这个项目的目标是确定再生的分子和细胞基础的再生的植物。 子宫内膜该领域的一个主要挑战是，人类属于一个非常小的哺乳动物群体， 去吧。因此，尽管动物模型推动了许多科学研究，但常见的动物模型如小鼠， 而大鼠在月经研究中的效用有限。这个项目使用常见的多刺鼠标，这是 只有已知的啮齿类动物，进行功能测试的要求，月经。同时，我们 将开发方法来确定人类子宫内膜如何随时间变化。使用这些方法， 我们的目标是了解青春期月经开始和重新开始时子宫内膜的变化， 怀孕后。拟议的研究非常适合新创新者计划，因为我们的理解 子宫内膜再生的研究远远落后于更普遍研究的再生器官。因此我们 必须承担战略风险，推动我们对月经进行更精确的机械理解， 这是一个迷人的过程，影响着大部分人口的生活。