Fertility Preservation in Monovulatory Species

单排物种的生育力保存

• 批准号: G0801261/1
• 负责人: Bruce Campbell
• 金额: $ 61.59万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801261%2F1
• 关键词: Fertility; Preservation; Monovulatory; Species

The ovary functions by periodically releasing an egg, grown within a follicle, which may then be fertilised. When the number of follicles is exhausted, the ovary ceases to function. Some medical treatments, such as chemo- and radiotherapies, destroy large numbers of follicles and prematurely cause the loss of ovarian function and fertility. One possible way of preventing this damage is to remove small pieces of ovarian tissue rich in follicles before treatment begins and preserve them by freezing to very low temperatures. The tissue can then be grafted back at a later date to resume function. Whilst this has been successful in both animals and humans, the length of time the tissue functions for is again determined by the number of follicles preserved in the graft which, in these small pieces of tissue, is limited. One way to improve this is to freeze whole ovaries, however considerable improvements are still required to minimise the damage currently seen following freeze-thawing and to achieve long-term ovarian function. Initial thoughts were that the freezing process and the lack of oxygen and nutrients supplied to the ovary during preparation for freezing and transplantation were causing this damage. However we have shown that this is not the case. As this technique is still relatively new, there remain several avenues of research to be explored and optimised to provide the most efficient method of freeze-thawing and grafting whole ovaries. This research initially aims to identify those areas which may be responsible for follicle damage and failure of frozen ovaries to being working again. This will then lead to a series of experiments looking at ways to correct the damage which may arise at each stage of the freeze, thaw and grafting processes to maximise ovarian and vascular tissue preservation. A variety of laboratory techniques will be used to study tissue structure, cell regeneration and gene expression in order to assess ovarian and vascular tissue health and damage. Finally, a study using sheep will implement all the improvements in technique developed over the course of the study and assess the relative value of the changes made in terms of the length of ovarian function, restoration of fertility and its possible clinical application in human fertility preservation. The overall aim is to improve the success of whole ovary freezing and bring it closer to becoming a viable option for the preservation of ovarian function in women.

卵巢的功能是周期性地释放卵子，卵子在卵泡中生长，然后受精。当卵泡的数量耗尽时，卵巢就停止了功能。一些医学治疗，如化疗和放疗，会破坏大量的卵泡，过早地导致卵巢功能和生育能力的丧失。防止这种损害的一种可能的方法是在治疗开始之前去除富含卵泡的小块卵巢组织，并通过低温冷冻保存它们。这些组织可以在以后移植回来恢复功能。虽然这种方法在动物和人类身上都取得了成功，但组织功能的长度再次取决于移植物中保存的卵泡数量，而在这些小块组织中，卵泡数量是有限的。改善这种情况的一种方法是冷冻整个卵巢，然而，仍需要进行相当大的改进，以尽量减少目前冻融后的损害，并实现卵巢的长期功能。最初的想法是，冷冻过程和卵巢在准备冷冻和移植过程中缺乏氧气和营养供应是造成这种损害的原因。然而，我们已经证明，情况并非如此。由于这项技术仍然相对较新，仍有一些研究途径有待探索和优化，以提供最有效的冷冻解冻和移植整个卵巢的方法。这项研究最初的目的是确定那些可能导致卵泡损伤和冷冻卵巢无法再次工作的区域。这将导致一系列的实验，寻找方法来纠正在冷冻、解冻和移植过程的每个阶段可能出现的损伤，以最大限度地保存卵巢和血管组织。多种实验室技术将用于研究组织结构，细胞再生和基因表达，以评估卵巢和血管组织的健康和损伤。最后，一项使用绵羊的研究将实现在研究过程中开发的技术的所有改进，并评估在卵巢功能长度，生育能力恢复及其在人类生育能力保存方面可能的临床应用方面所做的改变的相对价值。总的目标是提高整个卵巢冷冻的成功率，使其更接近于成为保存女性卵巢功能的可行选择。