Activation of human ovarian follicles and derivation of competent oocytes

女性生来就有卵子储备，这些卵子必须维持她们整个生育期。这些卵处于卵巢未成熟阶段，处于保护性囊状结构（卵泡）内，并处于静止状态，直到它们被激活生长。这一激活过程是决定女性生殖寿命和绝经时间的最重要因素。然而，关于这一过程在人类中是如何被调节的几乎一无所知，尽管它的破坏会导致卵巢早衰（POF）、不孕和相关的女性健康问题。这项研究着眼于激活是如何被调节的，以及如何操纵它来改变发育到可以受精阶段的卵子的数量和质量。我们现在能够在人体组织中解决这个问题，通过使用我们开发的一种支持体外卵泡激活的新型培养系统。利用这种方法，我们将研究两种机制（PTEN和mTORC1）的作用，这两种机制已被证明通过添加破坏（抑制/刺激）它们的因素来影响小鼠卵泡激活率。在这些操作之后，可以测试卵母细胞的发育和功能。所获得的结果可能会导致改善POF，不孕症的治疗方法以及调节女性生育能力的方法的发展。

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.