Pre-clinical Trials for Female Fertility Preservation
女性生育力保存的临床前试验
基本信息
- 批准号:6998863
- 负责人:
- 金额:$ 35.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-01-01 至 2008-12-31
- 项目状态:已结题
- 来源:
- 关键词:DNA damageMacaca mulattacesarean sectioncytoprotectiondrug delivery systemsdrug screening /evaluationegg /ovumembryogenesisfemalefertilityfertility promoting drugin vitro fertilizationlaparoscopymenstrual cyclemixed tissue /cell cultureneoplasm /cancer radiation therapynonhuman therapy evaluationovariectomyreproductive system disorder chemotherapysphingosinetherapy adverse effect
项目摘要
DESCRIPTION (provided by applicant): Early ovarian failure and infertility are well-known side effects of anti-cancer treatments. While the need for tumor eradication is clear, the long-term consequences of these treatments on non-target tissues, such as the ovaries, are substantial. Unfortunately, attempts to preserve fertility and ovarian function in female cancer patients have met with little success. In studies with mice, we have shown that sphingosine-1- phosphate (S1P), a metabolite of the pro-apoptotic stress sensor ceramide, completely protects the ovaries from radiation-induced damage in vivo. Long-term in vivo mating trials have further shown that S1P preserves a normal level of fertility in irradiated female mice, and that offspring conceived with oocytes protected from radiation by S1P in vivo show no evidence of transgenerational genomic damage. With the use of a human ovarian-mouse xenograft model, we have also shown that injecting S1P directly into ovarian tissue can prevent radiation-induced loss of human primordial and primary follicles in vivo. Although these findings support that S1P-based strategies could be developed to combat infertility and ovarian failure, two major points still need to be addressed. The first is to establish the safety and efficacy of S1P for preserving ovarian function and fertility in non-human primates exposed to anti-cancer treatments. The second is to validate technologies to deliver S1P only to the ovaries, thereby preventing systemic availability of S1P that could benefit the tumor cells targeted for destruction. To accomplish these goals, the following Specific Aims are proposed: (1) to determine if S1P can be administered directly into the rhesus monkey ovary as a means to protect the gonads from radiotherapy-induced damage in vivo; (2) to evaluate the competency of the oocytes protected from radiotherapy by S1P in the non-human primate ovary for fertilization and embryogenesis; and (3) to assess if offspring conceived from non-human primate oocytes protected from radiotherapy by S1P in vivo show evidence of propagated genomic damage. The goal of our work is to develop safe and effective strategies for protecting human ovaries in vivo from the side-effect damage caused by anti-cancer therapies. We believe that the published and preliminary data discussed herein strongly support the need for now evaluating the efficacy of, as well as the delivery mechanisms for, S1P in this regard using the non-human primate as a model.
描述(申请人提供):早期卵巢衰竭和不孕不育是众所周知的抗癌治疗的副作用。虽然根除肿瘤的必要性是显而易见的,但这些治疗对卵巢等非靶标组织的长期影响是巨大的。不幸的是,保留女性癌症患者生育能力和卵巢功能的尝试收效甚微。在对小鼠的研究中,我们已经证明,神经酰胺的代谢物鞘氨醇-1-磷酸(S1P)可以在体内完全保护卵巢免受辐射损伤。长期的体内交配试验进一步表明,S1P在受辐射的雌性小鼠中保持了正常的生育水平,而在体内用S1P保护的卵母细胞受孕的后代没有证据表明存在跨代基因组损伤。通过使用人卵巢-小鼠异种移植模型,我们还表明,在体内将S1P直接注射到卵巢组织中可以防止辐射诱导的人原始卵泡和初级卵泡的丢失。尽管这些发现支持可以开发基于S1P的策略来对抗不孕症和卵巢衰竭,但仍需要解决两个主要问题。首先是确定S1P在接受抗癌治疗的非人类灵长类动物中保护卵巢功能和生育能力的安全性和有效性。第二是验证仅将S1P输送到卵巢的技术,从而防止S1P在全身获得有利于目标肿瘤细胞的S1P。为了实现这些目标,提出了以下具体目标:(1)确定S1P是否可以直接注射到恒河猴卵巢中,作为一种在体内保护性腺免受放射损伤的手段;(2)评估S1P保护的非人类灵长类卵巢中的卵母细胞受精和胚胎发生的能力;以及(3)评估在体内S1P保护的非人灵长类卵母细胞受孕的后代是否显示出繁殖的基因组损伤的证据。我们工作的目标是开发安全有效的策略,以保护体内的人卵巢免受抗癌治疗所造成的副作用损害。我们认为,本文讨论的已发表的和初步的数据强烈支持现在需要使用非人类灵长类动物作为模型来评估S1P在这方面的有效性以及传递机制。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jonathan Lee Tilly其他文献
Jonathan Lee Tilly的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jonathan Lee Tilly', 18)}}的其他基金
Lineage tracing of germline stem cell differentiation in adult ovaries
成人卵巢生殖干细胞分化的谱系追踪
- 批准号:
8803589 - 财政年份:2013
- 资助金额:
$ 35.57万 - 项目类别:
Lineage tracing of germline stem cell differentiation in adult ovaries
成人卵巢生殖干细胞分化的谱系追踪
- 批准号:
8523188 - 财政年份:2012
- 资助金额:
$ 35.57万 - 项目类别:
Lineage tracing of germline stem cell differentiation in adult ovaries
成人卵巢生殖干细胞分化的谱系追踪
- 批准号:
8383164 - 财政年份:2012
- 资助金额:
$ 35.57万 - 项目类别:
Pre-clinical Trials for Female Fertility Preservation
女性生育力保存的临床前试验
- 批准号:
7334187 - 财政年份:2004
- 资助金额:
$ 35.57万 - 项目类别:
Pre-clinical Trials for Female Fertility Preservation
女性生育力保存的临床前试验
- 批准号:
6839400 - 财政年份:2004
- 资助金额:
$ 35.57万 - 项目类别:
Mechanisms of Female Germline Stem Cell Senescence
女性生殖干细胞衰老的机制
- 批准号:
6949892 - 财政年份:2004
- 资助金额:
$ 35.57万 - 项目类别:
Mechanisms of Female Germline Stem Cell Senescence
女性生殖干细胞衰老的机制
- 批准号:
6847621 - 财政年份:2004
- 资助金额:
$ 35.57万 - 项目类别:
Mechanisms of Female Germline Stem Cell Senescence
女性生殖干细胞衰老的机制
- 批准号:
7093142 - 财政年份:2004
- 资助金额:
$ 35.57万 - 项目类别:
Pre-clinical Trials for Female Fertility Preservation
女性生育力保存的临床前试验
- 批准号:
7154761 - 财政年份:2004
- 资助金额:
$ 35.57万 - 项目类别:
Pre-clinical Trials for Female Fertility Preservation
女性生育力保存的临床前试验
- 批准号:
6718229 - 财政年份:2004
- 资助金额:
$ 35.57万 - 项目类别:
相似国自然基金
基于多组学技术研究肠道微生物在猕猴(Macaca mulatta)衰老过程中的作用机制
- 批准号:32370450
- 批准年份:2023
- 资助金额:50 万元
- 项目类别:面上项目
猕猴(Macaca mulatta)衰老过程中凝血功能变化规律及基因表达调控机制研究
- 批准号:
- 批准年份:2020
- 资助金额:58 万元
- 项目类别:
太行山猕猴(Macaca mulatta tcheliensis)雌性的配偶选择
- 批准号:
- 批准年份:2020
- 资助金额:58 万元
- 项目类别:
猕猴(Macaca mulatta)亚种及其近缘种比较基因组学研究
- 批准号:31471989
- 批准年份:2014
- 资助金额:85.0 万元
- 项目类别:面上项目
相似海外基金
Effects of losartan on mitochondria and prediabetes in rhesus monkeys (Macaca mulatta)
氯沙坦对恒河猴(Macaca mulatta)线粒体和糖尿病前期的影响
- 批准号:
10084237 - 财政年份:2020
- 资助金额:
$ 35.57万 - 项目类别:
Defining the molecular signature of regeneration using single cell sequencing of Macaca Mulatta dorsal root ganglia neurons
使用猕猴背根神经节神经元的单细胞测序定义再生的分子特征
- 批准号:
338608 - 财政年份:2015
- 资助金额:
$ 35.57万 - 项目类别:
Fellowship Programs
Longitudinal Investigation of Maternal Influences on Infant Outcomes Mediated by Physiological Investment and Behavioral Care during Lactation in Rhesus Macaques (Macaca mulatta)
母体对哺乳期生理投入和行为护理介导的恒河猴(Macaca mulatta)婴儿结局影响的纵向调查
- 批准号:
0921978 - 财政年份:2009
- 资助金额:
$ 35.57万 - 项目类别:
Standard Grant
SYSTEMIC ARTERIOPATHY IN SIV-INFECTED RHESUS MACAQUES (MACACA MULATTA)
感染 SIV 的恒河猴 (MACACA MULATTA) 的系统性动脉病
- 批准号:
7562385 - 财政年份:2007
- 资助金额:
$ 35.57万 - 项目类别:
Evaluation of HIV-1 Vaccine Candidates in Macaca mulatta
HIV-1 候选疫苗在猕猴中的评价
- 批准号:
7166863 - 财政年份:2006
- 资助金额:
$ 35.57万 - 项目类别:
Transmissible Spongiforme Encephalopathy in non-human primate model after intraperitoneal sCJD-, vCJD-, and BSE-inoculation in the rhesus monkey (Macaca mulatta)
恒河猴(Macaca mulatta)腹腔内接种 sCJD、vCJD 和 BSE 后非人类灵长类动物模型中的传染性海绵状脑病
- 批准号:
5442913 - 财政年份:2005
- 资助金额:
$ 35.57万 - 项目类别:
Research Grants
RETINAL AGING IN MACACA MULATTA FROM PUERTO RICO
波多黎各猕猴的视网膜老化
- 批准号:
2706021 - 财政年份:1999
- 资助金额:
$ 35.57万 - 项目类别:
Zur Kooperation und Konkurrenz unter weiblichen Rhesusaffen (Macaca mulatta). Was bedeutet Verwandtschaft für Primaten: Vertrautheit oder gemeinsame Allele?
雌性恒河猴(Macaca mulatta)之间的合作与竞争。
- 批准号:
5186152 - 财政年份:1999
- 资助金额:
$ 35.57万 - 项目类别:
Research Grants
VISUAL SLIDES ON SELF INJURIOUS BEHAVIOR IN RHESUS MONKEYS (MACACA MULATTA)
关于恒河猴(MACACA MULATTA)自残行为的视觉幻灯片
- 批准号:
6277743 - 财政年份:1998
- 资助金额:
$ 35.57万 - 项目类别:
PANCREATIC ENDOCRINE NEOPLASM IN RHESUS MACAQUE (MACACA MULATTA)
恒河猴(MACACA MULATTA)胰腺内分泌肿瘤
- 批准号:
6247525 - 财政年份:1997
- 资助金额:
$ 35.57万 - 项目类别: