PHOSPHODIESTERASE 3 INHIBITORS: BLOCKERS OF OOCYTE MATURATION AND FERTILIZATION

磷酸二酯酶 3 抑制剂：卵母细胞成熟和受精的阻断剂

• 批准号: 8357748
• 负责人: JEFFREY T. JENSEN
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357748
• 关键词: Adverse effects; Affect; Attention; Biology; Chronic; Contraceptive Agents; Contraceptive methods; Cyclic GMP; Fertilization; Funding; Gonadotropins; Grant; Health Benefit; Macaca mulatta; Morals; National Center for Research Resources; Ovarian Stimulations; Ovary; Ovulation; Partner in relationship; Periodicity; Pregnancy; Primates; Principal Investigator; Protein Isoforms; Protocols documentation; Regulation; Research; Research Infrastructure; Research Methodology; Resources; Role; Source; United States National Institutes of Health; Unwanted Birth; abortion; corpus luteum; cost; in vivo; inhibitor/antagonist; novel; oocyte maturation; phosphoric diester hydrolase; prevent; selective expression; unintended pregnancy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Contraception provides significant preventative health benefits by reducing unintended pregnancy, abortions, and unwanted births. As side effects, access, and cultural or moral objections limit the universal acceptance of current methods, research into novel contraceptives is warranted. The purpose of this project is to explore the hypotheses that selective expression of phosphodiesterase (PDE) isoforms exists in the primate ovary, that selective blockade of the PDE3 isoform can be exploited to prevent spontaneous and gonadotropin-induced oocyte maturation, and that chronic treatment with a PDE3 inhibitor can prevent pregnancy in primates without affecting menstrual cyclicity or luteal function. The Specific Aims are to: (1) describe the basic biology of PDE expression in the primate ovary, (2) determine if PDE3 inhibitors prevent oocyte maturation, but not ovulation and function of the corpus luteum in rhesus monkeys undergoing controlled ovarian stimulation (COS) protocols or during natural cycles in vivo, and 3) determine whether PDE3 inhibitors function as contraceptive agents in regularly cycling rhesus monkeys in paired mating situations. In the final year of the grant, attention was also directed to the role of cGMP-medicated regulation of PDE3.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 避孕可以减少意外怀孕、流产和意外分娩，从而提供显着的预防性健康益处。由于副作用、获取途径以及文化或道德反对限制了当前方法的普遍接受，因此有必要研究新型避孕药具。该项目的目的是探索以下假设：灵长类动物卵巢中存在磷酸二酯酶（PDE）同工型的选择性表达，可以利用选择性阻断 PDE3 同工型来阻止自发和促性腺激素诱导的卵母细胞成熟，以及长期治疗PDE3 抑制剂可以防止灵长类动物怀孕，而不影响月经周期或黄体功能。 具体目标是：(1) 描述灵长类动物卵巢中 PDE 表达的基本生物学，(2) 确定 PDE3 抑制剂是否会阻止卵母细胞成熟，但不会阻止接受受控卵巢刺激 (COS) 的恒河猴的排卵和黄体功能) 方案或在体内自然周期期间，以及 3) 确定 PDE3 抑制剂是否在配对交配情况下定期循环的恒河猴中起到避孕作用。在资助的最后一年，cGMP 药物调节 PDE3 的作用也受到关注。