NOVEL CONTRACEPTIVES: CONTROL OF OOCYTE MATURATION

新型避孕药：控制卵母细胞成熟

• 批准号: 7715988
• 负责人: Xuemei Wu
• 金额: $ 1.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715988
• 关键词: Breeding; Chronic; Computer Retrieval of Information on Scientific Projects Database; Contraceptive Agents; Endocrine; Experimental Designs; Female; Foundations; Funding; Future; Genes; Grant; Human; In Vitro; Institution; Macaca; Macaca mulatta; Measurement; Meiosis; Menstrual cycle; Messenger RNA; Monkeys; Oocytes; Ovarian Stimulations; Ovary; Partner in relationship; Pathway interactions; Primates; Proteins; Purpose; RNA Interference; Research; Research Personnel; Resources; Source; Testing; Toxic effect; United States National Institutes of Health; contraceptive efficacy; contraceptive target; granulosa cell; in vivo; inhibitor/antagonist; novel; oocyte maturation; research study; selective expression

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. The purpose of this grant is to explore the hypotheses that selective expression of meiosis activating and inhibiting genes exists in the primate ovary, and that candidate molecules can be tested for contraceptive potential using an established sequence of in vitro and in vivo experiments culminating in a contraceptive trial in breeding groups of macaques. The Specific Aims are: (1) to identify ovary-expressed genes that may be related to oocyte maturation; and to investigate the in vitro functions of selected candidates (e.g, INSL3-LGR8 pathway, WEE1B, and oocyte-specific NLRPs), (2) to determine if selected candidates can be used as contraceptive agents in rhesus monkeys in vivo, and (3) to determine whether selected candidates (e.g., INSL3) can function as a contraceptive agents in regularly cycling rhesus monkeys in paired mating situations. Experimental designs will include: characterization of gene products (mRNA and protein) in the macaque ovary, in vitro RNAi in the oocyte and in vitro incubation of immature oocytes and granulosa cells with meiotic inhibitors and activators (Aim 1); in vivo administration of INSL3 or its antagonist to monkeys during controlled ovarian stimulation (COS) and spontaneous menstrual cycles, plus endocrine and toxicity measurements (Aim 2); and chronic administration of INSL3 or its inhibitor to fertile females in a breeding colony to assess contraceptive efficacy and long term toxicity (Aim 3). This approach is expected to provide a foundation for future trials of INSL3 in humans; and to identify other oocyte-specific novel gene products as potential future contraceptive targets.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这项资助的目的是探索以下假设：灵长类动物卵巢中存在减数分裂激活和抑制基因的选择性表达，并且可以使用已建立的体外和体内实验序列来测试候选分子的避孕潜力，最终产生避孕药在猕猴繁殖群体中进行试验。 具体目标是：（1）鉴定可能与卵母细胞成熟相关的卵巢表达基因；并研究所选候选物（例如 INSL3-LGR8 通路、WEE1B 和卵母细胞特异性 NLRP）的体外功能，（2）确定所选候选物是否可以在恒河猴体内用作避孕药，以及（3 ）以确定选定的候选物（例如 INSL3）是否可以在配对交配情况下定期循环的恒河猴中充当避孕药。 实验设计将包括：猕猴卵巢中基因产物（mRNA 和蛋白质）的表征、卵母细胞中的体外 RNAi 以及未成熟卵母细胞和颗粒细胞与减数分裂抑制剂和激活剂的体外培养（目标 1）；在受控卵巢刺激 (COS) 和自发月经周期期间对猴子进行 INSL3 或其拮抗剂体内给药，并进行内分泌和毒性测量（目标 2）；对繁殖群体中的可育雌性长期施用 INSL3 或其抑制剂，以评估避孕效果和长期毒性（目标 3）。 该方法有望为未来 INSL3 的人体试验奠定基础；并确定其他卵母细胞特异性新基因产物作为未来潜在的避孕目标。