ASSESSING OVARIAN RESERVE AFTER FOLLICULAR PROTECTION PRIOR TO X-IRRADIATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 卵巢衰竭是女孩和年轻女性接受放疗或化疗的常见副作用。鉴于生存率的提高，特别是在乳腺癌患者中，癌症治疗对生育力的长期影响是癌症后生活质量的重要考虑因素。目前正在开发保护卵巢免受癌症治疗不良影响的新策略。例如，在小鼠进行放射或化疗之前，卵巢直接暴露于鞘氨醇-1-磷酸(S1P)可维持卵泡及其封闭的卵母细胞的健康和功能不受损害，从而使受精和出生活体后代成为可能。这些研究已经扩展到非人类灵长类动物，在X-射线照射前卵巢内注射S1P或S1P激动剂可以保护一组卵泡，这些卵泡可以导致正常的卵巢/月经周期，产生能够植入前胚胎发育的成熟卵母细胞，以及没有DNA损伤的活后代。S1P激动剂提供卵巢保护的一个机制涉及通过干扰辐射诱导的细胞死亡途径来防止卵母细胞死亡。我们正在研究其他类型的卵巢细胞，即围绕卵母细胞和/或卵巢血管系统的卵泡细胞，是否也能幸免于S1P激动剂治疗猕猴的辐射毒性效应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ovarian failure is a common side-effect of radiation or chemotherapy treatment in girls and young women. In view of increasing survival rates, especially in breast cancer patients, long-term consequences of cancer treatments with respect to fertility are important considerations for quality of life after cancer. Novel strategies for protecting the ovaries from adverse effects of cancer therapies are currently under development. For example, direct ovarian exposure to sphingosine-1-phosphate (S1P) prior to radio-or chemotherapy in mice maintains the health and function of follicles and their enclosed oocytes from damage such that fertilization and birth of live offspring are possible. These studies have been extended to nonhuman primates wherein intraovarian infusion of S1P or S1P agonist prior to X-irradiation protects a cohort of follicles that leads to normal ovarian/menstrual cyclicity, production of mature oocytes capable of preimplantation embryonic development and live offspring devoid of DNA damage. One mechanism whereby S1P agonists confer ovarian protection involves the prevention of oocyte death by interference in the cell death pathway induced by radiation. We are investigating whether other ovarian cell types, i.e. follicular cells surrounding the oocyte and/or the ovarian vasculature, are also spared from the toxic effects of radiation with S1P agonist treatment in macaques.