PHOSPHODIESTERASE 3 INHIBITORS: SELECTIVE BLOCKERS OF OOCYTE MATURATION AND FERT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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当前避孕方法的普遍接受，因此有必要研究新的避孕方法。本基金的目的是探索灵长类动物卵巢中存在选择性表达磷酸二酯酶（PDE）异构体的假设，PDE3的选择性阻断可以用来阻止自发和促性腺激素诱导的卵母细胞成熟，以及PDE3抑制剂的慢性治疗可以在不影响月经周期或黄体功能的情况下防止灵长类动物怀孕。具体目的是：(1)描述PDE在灵长类动物卵巢中的基本生物学表达；(2)确定PDE3抑制剂是否在体内进行可控卵巢刺激（COS）或自然周期的恒河猴中阻止卵母细胞成熟，但不阻止排卵和黄体功能；(3)确定PDE3抑制剂在定期循环的恒河猴配对交配情况下是否具有避孕作用。

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. 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 grant is to explore the hypotheses that selective expression of phosphodiesterase (PDE) isoforms exists in the primate ovary, that selective blockade of PDE3 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) to 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) to determine whether PDE3 inhibitors function as contraceptive agents in regularly cycling rhesus monkeys in paired mating situations.