PHOSPHODIESTERASE 3 INHIBITORS: BLOCKERS OF OOCYTE MATURATION AND FERTILIZATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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、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。这笔赠款的目的是探索以下假设：灵长类卵巢中存在选择性表达磷酸二酯酶(PDE)亚型，选择性阻断PDE3可用于防止自发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卵母细胞成熟，但不会阻止接受控制性卵巢刺激(COS)方案或体内自然周期的恒河猴的排卵和黄体功能；以及(3)确定PDE3抑制剂在配对交配情况下是否可作为避孕剂用于定期周期的恒河猴。

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.