PHOSPHODIESTERASE 3 INHIBITORS: BLOCKERS OF OOCYTE MATURATION AND FERTILIZATION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 避孕通过减少意外怀孕、堕胎和意外生育，提供了显著的预防性健康益处。由于副作用、可获得性和文化或道德上的反对意见限制了人们对当前方法的普遍接受，因此有必要研究新的避孕方法。该项目的目的是探索以下假设：灵长类卵巢中存在磷酸二酯酶(PDE)亚型的选择性表达，选择性阻断PDE3亚型可以防止自发的和促性腺激素诱导的卵母细胞成熟，以及长期使用PDE3抑制剂可以在不影响月经周期或黄体功能的情况下阻止灵长类动物的怀孕。其具体目的是：(1)描述PDE在灵长类卵巢中表达的基本生物学；(2)确定PDE3抑制剂是否可以阻止受控卵巢刺激(COS)方案或体内自然周期中的恒河猴卵母细胞成熟，但不阻止排卵和黄体功能；以及3)确定PDE3抑制剂是否在配对交配情况下作为避孕剂作用于定期周期的恒河猴。在赠款的最后一年，还将注意力转向cGMP对PDE3的药物调控的作用。

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.