PRE-CLINICAL TRIALS FOR FEMALE FERTILITY PRESERVATION

女性生育力保存的临床前试验

• 批准号: 8173193
• 负责人: Mary B Zelinski
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173193
• 关键词: Adverse effects; Apoptotic; Biological Preservation; Cancer Patient; Ceramides; Computer Retrieval of Information on Scientific Projects Database; Embryonic Development; Failure; Female; Fertility; Fertilization; Funding; Genomics; Goals; Gonadal structure; Grant; Human; Infertility; Institution; Macaca; Macaca mulatta; Mus; Oocytes; Ovarian; Ovary; Primates; Radiation; Radiation induced damage; Radiation therapy; Research; Research Personnel; Resources; Safety; Source; Stress; Technology; Tissues; United States National Institutes of Health; Validation; base; cancer therapy; combat; in vivo; meetings; neoplastic cell; offspring; preclinical study; prevent; sensor; sphingosine 1-phosphate; success

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. Early ovarian failure and infertility are well-known side effects of anti-cancer treatments. The long-term consequences of these treatments on non-target tissues, such as the ovaries are substantial. Attempts to preserve fertility and ovarian function in female cancer patients have met with little success. In mice, sphingosine-1-phosphate (S1P), a metabolite of the pro-apoptotic stress sensor ceramide, completely protects the ovaries from radiation-induced damage in vivo. In vivo, S1P preserves a normal level of fertility in irradiated female mice, and offspring conceived with oocytes protected from radiation by S1P show no evidence of transgenerational genomic damage. Thus, S1P-based strategies could be developed to combat infertility and ovarian failure. The safety and efficacy of S1P for preserving ovarian function and fertility in primates exposed to anti-cancer treatments needs to be established. Technologies to deliver S1P only to the ovaries, thereby preventing systemic availability of S1P that could benefit the tumor cells targeted for destruction, also requires validation. The specific aims are 1) to determine if S1P can be administered directly into the rhesus monkey ovary to protect the gonads from radiotherapy-induced damage in vivo; 2) to evaluate the competency of macaque oocytes protected from radiotherapy by S1P for fertilization and embryogenesis; and 3) to assess if offspring conceived from macaque oocytes protected from radiotherapy by S1P in vivo show evidence of propagated genomic damage. The long-term goal is to develop safe and effective strategies for protecting human ovaries in vivo from the side-effect damage caused by anti-cancer therapies, and prevent infertility.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 早期的卵巢衰竭和不育是抗癌治疗的众所周知的副作用。这些治疗对非目标组织的长期后果（例如卵巢）是很大的。 女性癌症患者的生育能力和卵巢功能的尝试几乎没有成功。 在小鼠中，鞘氨醇1-磷酸（S1P），一种促凋亡应力传感器神经酰胺的代谢产物， 完全保护卵巢免受辐射引起的体内损伤。 在体内，S1P保留了受辐照的雌性小鼠的正常生育能力，并以S1P保护的卵母细胞构想的后代没有跨代基因组损伤的证据。 因此，可以制定基于S1P的策略来打击不育和卵巢失败。 需要确定S1P对维护卵巢功能和暴露于抗癌治疗的灵长类动物的生育能力的安全性和功效。 仅向卵巢传递S1P的技术，从而防止S1P的全身性可用性，该S1可能受益于针对破坏的肿瘤细胞 需要验证。 具体目的是1）确定是否可以直接将S1P施用到恒河猴卵巢中，以保护性腺免受放疗诱导的体内损伤； 2）评估S1P免受放射疗法保护的猕猴的能力； 3）评估S1P在体内保护免于放射疗法的猕猴的后代是否显示出基因组损伤的证据。 长期目标是制定安全有效的策略，以保护体内人类卵巢免受抗癌疗法造成的副作用损害，并防止不孕症。