PHOSPHODIESTERASE 3 INHIBITORS: BLOCKERS OF OOCYTE MATURATION AND FERTILIZATION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 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、获取途径以及文化或道德上的反对限制了对当前方法的普遍接受，因此有必要对新型避孕药进行研究。本项目的目的是探索以下假设：在灵长类动物卵巢中存在磷酸二酯酶（PDE）亚型的选择性表达，可以利用PDE 3亚型的选择性阻断来防止自发和促性腺激素诱导的卵母细胞成熟，以及用PDE 3抑制剂长期治疗可以防止灵长类动物妊娠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PDE 3抑制剂是否阻止卵母细胞成熟，但不阻止经历控制性卵巢刺激（COS）方案或在体内自然周期期间的恒河猴中的排卵和黄体功能，和3）确定PDE 3抑制剂是否在配对交配情况下在规律周期的恒河猴中作为避孕剂起作用。在拨款的最后一年，人们还关注了cGMP对PDE 3的调节作用。

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.