Systematic investigation of the effect of chemotherapeutic agents on the ovary using ovarian follicle culture systems.

使用卵泡培养系统系统研究化疗药物对卵巢的影响。

• 批准号: G1002118/1
• 负责人: Norah Spears
• 金额: $ 90.19万
• 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: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1002118%2F1
• 关键词: Systematic; investigation; effect; chemotherapeutic; agents

Many women undergoing chemotherapy treatment for cancer subsequently suffer from premature ovarian failure, and hence infertility. With recent advances in treatment resulting in greatly improved cancer survival rates, it is becoming increasingly important to counter adverse effects of treatment such as ovarian failure and infertility. Breast cancer patients are the most common group affected: 25% of these patients are pre-menopausal at the time of diagnosis and treatment will affect ovarian function in around half of these women. Loss of fertility can be a vital issue, but even where that is not the case, early onset of the menopause, with all of its accompanying adverse effects, is an important consideration for longer-term health care. While effects on the ovary are known to result from damage to ovarian follicles, the structures containing the eggs, it is not known what stages of follicle, or what cell types within the follicle, the chemotherapy drugs initially damage. This application proposes to use tissue culture techniques with isolated ovarian follicles, methods in which we have a great deal of expertise, to investigate this problem. We will investigate the precise stages of development of ovarian follicles at which they are most sensitive to different chemotherapy drugs, which cells within the follicle are the main site of damage from chemotherapy, and how this damage may indirectly affect other follicles growing within the ovary. We believe that this will be a powerful way forward that will, in the longer term, allow clinicians to test and compare the levels of damage to the ovary of a range of chemotherapy drugs, and provide the information necessary to facilitate ways of preventing ovarian failure.

许多接受癌症化疗的妇女随后患有卵巢早衰，因此不孕。随着治疗的最新进展大大提高了癌症的生存率，对抗治疗的不良反应如卵巢功能衰竭和不孕症变得越来越重要。乳腺癌患者是最常见的受影响群体：这些患者中有25%在诊断时处于绝经前，治疗将影响约一半女性的卵巢功能。生育能力丧失可能是一个至关重要的问题，但即使不是这种情况，更年期的早期发作及其伴随的所有不利影响也是长期保健的重要考虑因素。虽然已知对卵巢的影响是由于对卵泡（包含卵子的结构）的损伤，但尚不清楚卵泡的哪个阶段或卵泡内的细胞类型，化疗药物最初会损害。本申请建议使用组织培养技术与孤立的卵泡，方法中，我们有大量的专业知识，调查这个问题。我们将研究卵泡发育的确切阶段，在这些阶段，它们对不同的化疗药物最敏感，卵泡内的哪些细胞是化疗损伤的主要部位，以及这种损伤如何间接影响卵巢内生长的其他卵泡。我们相信，这将是一个强有力的前进方向，从长远来看，将允许临床医生测试和比较一系列化疗药物对卵巢的损伤水平，并提供必要的信息，以促进预防卵巢衰竭的方法。