ASSESSING OVARIAN RESERVE AFTER FOLLICULAR PROTECTION PRIOR TO X-IRRADIATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 卵巢功能衰竭是女孩和年轻女性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，癌症治疗对生育能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，在小鼠中，在放疗或化疗之前将卵巢直接暴露于鞘氨醇-1-磷酸（S1 P），可维持卵泡及其封闭的卵母细胞的健康和功能免受损害，从而使受精和活后代的出生成为可能。 这些研究已经扩展到非人灵长类动物，其中在X射线照射前卵巢内输注S1 P或S1 P激动剂保护一组卵泡，导致正常的卵巢/月经周期和能够植入前胚胎发育的成熟卵母细胞的产生。 虽然可以使用超声观察窦卵泡，但在癌症治疗后剩余的代表卵巢储备的生长的窦前卵泡的数量不能在体内直接量化。 因此，需要一种非侵入性的方法来预测卵巢保护后癌症患者的卵巢储备。抗苗勒管激素（AMH），由窦前卵泡的颗粒细胞产生，和卵泡素B（INHB），由窦卵泡的颗粒细胞产生，被用来评估妇女的卵巢储备希望辅助生殖技术怀孕。 我们正在研究这些激素的效用，以衡量卵巢储备癌症治疗后的纵向比较循环水平前和后X射线照射恒河猴接受S1 P为基础的卵巢保护。

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 and production of mature oocytes capable of preimplantation embryonic development. Although antral follicles can be observed using ultrasound, the number of growing preantral follicles remaining after cancer treatment, that represent ovarian reserve, cannot be quantified directly in vivo. Therefore, a non-invasive method for predicting ovarian reserve in cancer patients after ovarian protection is needed. Anti-mullerian hormone (AMH), produced by granulosa cells of preantral follicles, and inhibin B (INHB), produced by granulosa cells of antral follicles, are being used to assess ovarian reserve in women desiring assisted reproductive technologies for pregnancy. We are investigating the utility of these hormones to measure ovarian reserve after cancer treatment with longitudinal comparisons of circulating levels pre- and post-X-irradiation in rhesus monkeys receiving S1P-based ovarian protection.