Activation of human ovarian follicles and derivation of competent oocytes

人卵巢滤泡的激活和有能力卵母细胞的衍生

• 批准号: G0901839/1
• 负责人: Evelyn Telfer
• 金额: $ 62.22万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0901839%2F1
• 关键词: Activation; human; ovarian; follicles; derivation

Women are born with a store of eggs that must last them throughout their reproductive life. These eggs are in the ovary at an immature stage within protective sac like structures (follicles) and held in a resting state until they are activated to grow. This process of activation is the most important factor that determines a womans reproductive lifespan and when she will enter menopause. However, almost nothing is known about how this process is regulated in humans although its disruption can lead to Premature Ovarian Failure (POF), infertility and associated female health problems.This study is looking at how activation is regulated and how it can be manipulated to alter the number and quality of eggs that develop to the stage where they can be fertilised. We are now able to tackle this problem in human tissue by using a novel culture system that we have developed that supports activation of follicles outside the body. Using this we will investigate the role of two mechanisms (PTEN and mTORC1) that have been shown to affect the rate of follicle activation in mice by adding factors that disrupt (inhibit/stimulate) them. Oocyte development and function can then be tested after these manipulations. The results obtained could lead to improved treatments for POF, infertility as well as development of methods to regulate female fertility.

女性出生时就有一定的卵子储备，这些卵子必须在整个生殖过程中持续存在。这些卵子在卵巢中处于保护性囊状结构（卵泡）内的未成熟阶段，并保持静止状态，直到它们被激活生长。这个激活过程是决定女性生殖寿命以及何时进入更年期的最重要因素。然而，几乎没有人知道这个过程是如何在人类中调节的，尽管它的破坏可能导致卵巢早衰（POF），不孕症和相关的女性健康问题。这项研究正在研究激活是如何调节的，以及如何操纵它来改变卵子的数量和质量，这些卵子发育到可以受精的阶段。我们现在能够在人体组织中解决这个问题，方法是使用我们开发的一种新的培养系统，该系统支持体外卵泡的激活。利用这一点，我们将研究两种机制（PTEN和mTORC 1）的作用，这两种机制已被证明通过添加破坏（抑制/刺激）它们的因子来影响小鼠卵泡激活的速率。然后可以在这些操作之后测试卵母细胞发育和功能。所获得的结果可能会导致POF，不孕症的治疗方法的改进以及调节女性生育能力的方法的发展。