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

许多接受癌症化疗的妇女随后遭受卵巢早衰，从而导致不孕不育。随着最近治疗方法的进步大大提高了癌症存活率，对抗卵巢衰竭和不孕不育等治疗的不利影响变得越来越重要。乳腺癌患者是最常见的受影响人群：25%的患者在确诊时处于绝经前，治疗将影响大约一半的女性的卵巢功能。生育力丧失可能是一个至关重要的问题，但即使不是这样，更年期早期开始及其所有伴随的不利影响，也是长期医疗保健的一个重要考虑因素。虽然已知对卵巢的影响是由于对卵巢卵泡(包含卵子的结构)的损害，但尚不清楚化疗药物最初损害的是卵泡的哪个阶段或卵泡内的什么细胞类型。这项申请提出使用组织培养技术来研究这一问题，我们在这方面拥有丰富的专业知识。我们将调查卵泡发育的确切阶段，在哪个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的主要损害部位，以及这种损害可能如何间接影响卵巢内生长的其他卵泡。我们相信，从长远来看，这将是一个强有力的前进方向，将允许临床医生测试和比较一系列化疗药物对卵巢的损害程度，并提供必要的信息，以促进预防卵巢衰竭的方法。

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.