NOVEL CONTRACEPTIVES: CONTROL OF FOLLICULAR MATURATION AND RUPTURE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 雌性哺乳动物卵巢的主要功能是在动物的生殖寿命期间及时释放可受精的配子，即卵母细胞或卵子，尽管卵巢产生性类固醇激素。 这一功能通过排卵过程实现，其中完全发育的卵泡响应于排卵促性腺激素激增的作用而破裂，并释放卵丘-卵母细胞复合体以进入生殖道并可能受精。 然而，卵泡破裂和卵丘-卵母细胞复合体从卵泡的内（颗粒）细胞层脱离需要通过复杂的蛋白酶系统进行显著的细胞重组和细胞外基质重塑。 脱落之前，细胞与细胞之间的接触必须消失，卵丘细胞之间形成富含透明质酸的细胞外基质，导致卵丘-卵母细胞复合体大量增加或“扩张”。 此外，最近从非灵长类动物物种的数据表明，卵丘卵母细胞扩增（C-OE）涉及卵母细胞，颗粒/卵丘，和血清衍生因子之间的复杂的相互作用，如有针对性地破坏关键成分损害排卵和受精。 这些发现与新概念一致，即有可能选择性地抑制卵泡蛋白水解、C-OE、卵母细胞释放，从而抑制生育能力，而不改变女性生殖的其他方面，包括卵巢/月经周期。 因此，本项目的目的是测试的假设，蛋白酶，卵母细胞和颗粒/卵丘衍生蛋白控制卵泡破裂和C-OE在灵长类动物。 此外，还将确定阻断它们的合成或作用是否会阻止旧大陆（猕猴）猴中及时的C-OE、卵母细胞释放和妊娠。

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. The principal function of the ovary in female mammals, the production of sex steroid hormones notwithstanding, is to release the fertilizable gamete, the oocyte or egg, in a timely manner during the animal's reproductive lifespan. This function is achieved through the process of ovulation, wherein a fully-developed follicle ruptures in response to the actions of the ovulatory gonadotropin surge, and releases the cumulus-oocyte complex for passage into the reproductive tract and possible fertilization. However, follicle rupture and detachment of the cumulus-oocyte complex from the inner (granulosa) cell layer of the follicle requires significant cellular reorganization and extracellular matrix remodeling via a complex system of proteases. Detachment must be preceded by loss of cell-cell contacts and formation of a hyaluronan-rich extracellular matrix between cumulus cells, resulting in a large increase or "expansion" of the cumulus-oocyte complex. Furthermore, recent data from nonprimate species indicate that cumulus-oocyte expansion (C-OE) involves complex interactions between oocyte-, granulosa/cumulus-, and serum-derived factors, such that targeted disruption of key components impairs ovulation and fertilization. These findings are consistent with the novel concept that it is possible to selectively inhibit follicle proteolysis, C-OE, oocyte release, and hence fertility, without altering other aspects of female reproduction, including ovarian/menstrual cyclicity. Thus the objective of this project is to test the hypothesis that proteases, oocyte- and granulosa/cumulus-derived proteins control follicle rupture and C-OE in primates. Furthermore, it will be determined whether blockade of their synthesis or action will prevent timely C-OE, oocyte release and pregnancy in Old World (macaque) monkeys.