NOVEL CONTRACEPTIVES: CONTROL OF OOCYTE MATURATION

新型避孕药：控制卵母细胞成熟

基本信息

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
项目类别：
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

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

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项目摘要

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。这笔赠款的目的是探索在灵长类动物卵巢中有选择性表达激活和抑制基因的假设，并且可以使用既定的体外和体内实验中的既定序列进行避孕潜力来测试候选分子，从而获得避孕潜力。具体目的是：（1）识别可能与卵母细胞成熟有关的卵巢表达基因； 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猴子在配对的情况下。实验设计将包括：猕猴卵巢中基因产物（mRNA和蛋白）的表征，体外RNAi在卵母细胞中的体外RNAi以及未成熟卵母细胞和颗粒细胞与减数分裂抑制剂和活化剂的体外孵育（AIM 1）；在受控的卵巢刺激（COS）和自发月经周期中，在体内给药INSL3或其对猴子的拮抗剂，以及内分泌和毒性测量值（AIM 2）；以及长期对INSL3或其抑制剂的施用，以在繁殖菌落中肥沃的女性，以评估避孕功效和长期毒性（AIM 3）。预计这种方法将为INSL3在人类中的未来试验提供基础。并确定其他卵母细胞特异性的新基因产物作为潜在的未来避孕靶标。