Oocyte quality in health and disease

体外受精(IVF)和相关技术仍然相对低效和昂贵，随着产妇年龄的增加，这些问题变得更加严重。成功率低的主要原因之一是卵母细胞(卵子)质量差，因为我们对哺乳动物卵子发育的生物学和使卵子受精的因素(S)知之甚少。可用于研究的人类卵子有限，加剧了这一问题。为了提高辅助受孕治疗的成功率，我们需要最大限度地增加从女性身上收集的优质卵子的数量--S的卵巢，但我们必须注意，卵子质量不会以牺牲卵子数量为代价。因此，目前辅助受孕的趋势是从每个患者身上产生少量的好卵子，从而最大限度地改变他们的受孕状态。然而，只有当我们找到最适合试管受精的卵子，并利用这些信息来改进患者的治疗，从而使卵子质量最大化时，这一目标才能实现。因此，该项目的目标是测量健康妇女的卵子质量，并利用这些信息建立具有明确不孕症原因的患者的卵子健康的细胞和分子特征。该项目的目标是：(1)定义和连接鸡蛋质量的生化和代谢标记；(2)研究一些可能有助于鸡蛋健康的关键基因；以及(3)测量不同辅助生殖治疗制度对鸡蛋质量的影响。这项研究的某些方面将使用奶牛卵子进行，因为这些组织是人类卵子发育的良好模型；该项目的其他部分将使用为不孕症患者捐赠的人类卵子进行研究。我们已经开发并验证了鸡蛋蛋白质周转和能量代谢的分子生物学方法和分析，将用于该项目的鸡蛋质量检测。拟议研究产生的数据将极大地促进我们对人类卵子生物学的理解，并最终将有助于降低辅助受孕治疗的成本和提高成功率。

In vitro fertilisation (IVF) and associated technologies remain relatively inefficient and costly and the problems worsen with increasing maternal age. One of the main reasons for these low success rates is poor oocyte (egg) quality, as we know very little about the biology of mammalian egg development and the factor(s) which make eggs fertile. This issue is exacerbated by the limited available of human eggs for research. In order to improve the success of assisted conception treatments we need to maximise the number of good quality eggs we collect from a woman?s ovaries but we must be careful that egg quality does not suffer at the expense of egg quantity. The current momentum in assisted conception is therefore to produce a small number of good eggs from each patient and so maximise their change of a pregnancy. However, this goal can only be achieved if we can identify the best eggs for IVF and use this information to improve patient treatments and so maximise egg quality. The objective of this project is therefore to measure egg quality in healthy women and to use this information to establish a cellular and molecular signature of egg health from patients with defined causes of infertility. The project aims to: (1) define and link biochemical and metabolic markers of egg quality; (2) investigate a number of key genes which may contribute to egg health; and (3) measure the impact of different assisted reproduction treatment regimes on egg quality. Some aspects of the research will be conducted using cow eggs as these tissues are a good model for human egg development; other components of the project will be conducted using human eggs which have been donated for research by infertility patients. We have already developed and validated the molecular biology methods and assays of egg protein turnover and energy metabolism which will be utilised on this project to measure egg quality. The data generated by the proposed studies will significantly advance our understanding of human egg biology and will ultimately help reduce the cost and improve the success rates of assisted conception treatments.