Contraception by Blockade of Periovulatory Events in Primates

灵长类动物通过阻断排卵期事件来避孕

• 批准号: 7276989
• 负责人: RICHARD L STOUFFER
• 金额: $ 120万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-31 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276989
• 关键词: Address; Adult; Animals; Cells; Cercopithecidae; Cervical; Clinical; Collaborations; Contraceptive Agents; Contraceptive methods; Development; Drug Industry; Drug effect disorder; Embryo; Endopeptidases; Estrogens; Event; Evolution; Female; Fertility; Fertilization; Fostering; Gene Expression; Germ Cells; Health Sciences; Health Services Research; Human; Macaca; Meiosis; Menstrual cycle; Methods; Modality; Molecular; Monkeys; National Institute of Child Health and Human Development; Nuclear; Oocytes; Oregon; Ovarian; Ovary; Ovulation; Peptide Hydrolases; Physiological; Primates; Process; Proteins; Purpose; Recruitment Activity; Regulation; Reproduction; Reproductive Health; Reproductive system; Research; Research Personnel; Research Project Grants; Rodent Model; Rupture; Scientist; Selective Estrogen Receptor Modulators; Sperm Transport; System; Targeted Research; Testing; Translational Research; Universities; Validation; Woman; career; clinically relevant; concept; contraceptive efficacy; egg; gamete transport; interest; male; next generation; nonhuman primate; novel; oocyte maturation; pre-clinical; prevent; programs; reproductive; research and development; research study; response

DESCRIPTION (provided by applicant): The Oregon National Primate Research Center (ONPRC) proposes to establish a U54 Contraceptive Development Research Center that targets the discovery and development of novel contraceptive agents that prevent one or more periovulatory events in adult, female primates during the menstrual cycle. Four research projects and one animal core utilize Old World (macaque) monkeys to generate new information and proof-of-concept regarding potential modalities for preventing oocyte fertilization, and hence fertility, in women. Project I, "Control of Oocyte Maturation", will address the hypothesis that novel follicle cell- and oocyte-derived proteins control nuclear and cytoplasmic maturation of the oocyte, and can be exploited to prevent timely egg maturation and hence fertility during the menstrual cycle. Project II, "Control of Cumulus- Oocyte Expansion", will analyze the granulosa/cumulus cell- and oocyte-derived proteins controlling cumulus-oocyte expansion (C-OE) and test whether specific antagonists disrupt C-OE and hence egg release and fertility in female monkeys. Project III, "Control of Follicle Rupture", explores the unique proteases expressed in the periovulatory follicle in primates, and whether their inhibition will prevent ovulation and hence egg release and fertility during the menstrual cycle. Project IV, "Control of Gamete Transport and Fertilization", tests the hypothesis that estrogen action is essential for normal oviductal and cervical function, such that a selective estrogen receptor modulator (SERM) will disrupt oocyte and sperm transport within the reproductive tract, and hence prevent fertilization and fertility in macaques. Whereas basic discovery and elucidation of drug action will be pursued in each Project, promising agents will be tested in the Nonhuman Primate Contraceptive Core for contraceptive efficacy and reversibility, using small groups (10 females to 1-2 males) of macaques in controlled trials. The Administrative Core will foster intra- and inter-center cooperation in contraceptive research, and liaison with the NICHD Project Officer. The U54 CDRC will synergize with existing excellence in reproductive research at ONPRC and the Oregon Health & Science University (OHSU), including several available research service cores and existing ties with the pharmaceutical industry, to promote translational research of direct relevance to testing and formulating novel contraceptives in women.

描述(由申请人提供)：俄勒冈州国家灵长类动物研究中心(ONPRC)建议建立一个U54避孕发展研究中心，旨在发现和开发新型避孕药，防止成年雌性灵长类动物在月经周期中发生一种或多种排卵事件。四个研究项目和一个动物核心利用东半球(猕猴)猴子来产生关于预防妇女卵母细胞受精从而生育的潜在方式的新信息和概念验证。项目I“控制卵母细胞成熟”将解决这样的假设，即新的卵泡细胞和卵母细胞衍生蛋白控制卵母细胞的核和细胞质成熟，并可用于防止卵子及时成熟，从而防止月经周期中的生育。项目二“控制卵丘-卵母细胞扩张”将分析控制卵丘-卵母细胞扩张(C-OE)的颗粒/卵丘细胞和卵母细胞衍生蛋白，并测试特定的拮抗剂是否干扰C-OE，从而干扰雌性猴子的卵子释放和繁殖力。项目III，“控制卵泡破裂”，探索在灵长类动物排卵周卵泡中表达的独特的蛋白水解酶，以及抑制它们是否会阻止排卵，从而阻止月经周期中的卵子释放和生育。项目四，“控制配子运输和受精”，验证了雌激素作用对正常输卵管和宫颈功能至关重要的假设，即选择性雌激素受体调节剂(SERM)将扰乱卵子和精子在生殖道内的运输，从而阻止猕猴受精和生育。虽然每个项目都将寻求药物作用的基本发现和阐明，但有希望的药物将在非人类灵长类避孕药核心中进行避孕效果和可逆性的测试，在对照试验中使用一小群猕猴(10只雌性到1-2只雄性)。行政核心将促进中心内和中心间在避孕研究方面的合作，并与NICHD项目官员联络。U54 CDRC将与ONPRC和俄勒冈健康与科学大学(OHSU)现有的优秀生殖研究相结合，包括几个现有的研究服务核心和与制药行业的现有联系，以促进与女性测试和制定新型避孕药直接相关的转化性研究。