Biological foundation for epigenetic investigations of ART derived human oocytes and embryos

ART 衍生的人类卵母细胞和胚胎表观遗传学研究的生物学基础

• 批准号: G0701388/1
• 负责人: Helen Picton
• 金额: $ 65.24万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701388%2F1
• 关键词: Biological; foundation; epigenetic; investigations; ART

A growing body of evidence suggests that some of the technologies used to treat infertility in humans and/or the infertility itself may compromise the function of key genes which are associated with imprinting. The imprint is a unique mark found on a small number of genes. The imprint is established during the growth of eggs and sperm and it is vital for the development of healthy embryos before they implant to produce a pregnancy. Importantly, the imprinted mark can, in some cases, be changed erroneously during the laboratory procedures used to treat infertility. Errors in how the gene imprints are established and read may predispose an individual to diseases such as cancer and/or specific disorders associated with imprinted gene disruption including rare mental retardation syndromes such as Angelman syndrome, and Beckwith-Wiedemann syndrome. This is a major cause of concern as over a million babies have been born worldwide following assisted conception. Furthermore, it is possible that the more invasive assisted reproductive technologies (ART) which are increasingly being developed and used to treat infertile patients may predispose human embryos and the children born subsequently to imprinting errors. It is therefore of paramount importance to understand how imprinted genes work in healthy human eggs, sperm and embryos and to investigate how their programming can go wrong. This project will predominantly use highly sensitive and sophisticated molecular biology tools called microarrays and follow-up analyses to simultaneously study multiple imprinted genes and their regulators throughout the development of human eggs and embryos. The information generated by these unique studies will be used to confirm the safety of a new treatment for the in vitro growth of eggs- a technique which involves an extended period of culture in the laboratory during which time the eggs are ripened before they are fertilised. It is anticipated that status of the imprinted genes and their regulators can be used to test the safety of new ARTs, such as the in vitro maturation of oocytes, before they are introduced into routine clinical practise. The proposed work will therefore help us to understand and hopefully prevent imprinting errors and diseases being passed onto the next generation of children born following assisted conception.

越来越多的证据表明，一些用于治疗人类不育症的技术和/或不育症本身可能会损害与印记相关的关键基因的功能。印记是在少数基因上发现的独特标记。这种印记是在卵子和精子的生长过程中建立的，它对健康胚胎的发育至关重要，然后才能植入怀孕。重要的是，在某些情况下，在用于治疗不孕症的实验室程序中，印记标记可能会被错误地改变。基因印记如何建立和读取的错误可能使个体易患疾病，如癌症和/或与印记基因破坏相关的特定疾病，包括罕见的精神发育迟滞综合征，如Angelman综合征和Beckwith-Wiedemann综合征。这是一个令人关注的主要原因，因为全世界有超过一百万婴儿在辅助受孕后出生。此外，越来越多地被开发和用于治疗不孕症患者的更具侵入性的辅助生殖技术（ART）可能使人类胚胎和随后出生的儿童容易出现印记错误。因此，了解印记基因如何在健康的人类卵子、精子和胚胎中发挥作用，并研究它们的编程如何出错，是至关重要的。该项目将主要使用称为微阵列和后续分析的高灵敏度和复杂的分子生物学工具，同时研究人类卵子和胚胎发育过程中的多个印记基因及其调控因子。这些独特的研究所产生的信息将用于确认一种新的卵子体外生长治疗方法的安全性-这种技术涉及在实验室中进行长时间的培养，在此期间卵子在受精前成熟。预计印迹基因及其调节剂的状态可用于测试新ART的安全性，例如在将其引入常规临床实践之前，卵母细胞的体外成熟。因此，拟议的工作将有助于我们了解并希望防止印迹错误和疾病传递给辅助受孕后出生的下一代儿童。