NOVEL CONTRACEPTIVES: CONTROL OF FOLLICULAR MATURATION AND RUPTURE

新型避孕药：控制卵泡成熟和破裂

• 批准号: 8173236
• 负责人: Jon D Hennebold
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173236
• 关键词: Animals; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Contraceptive Agents; Data; Extracellular Matrix; Female; Fertility; Fertilization; Funding; Germ Cells; Gonadal Steroid Hormones; Gonadotropins; Grant; Hyaluronan; Institution; Longevity; Macaca; Mammals; Monkeys; Oocytes; Ovarian; Ovary; Ovulation; Peptide Hydrolases; Periodicity; Pregnancy; Primates; Process; Production; Proteins; Proteolysis; Reproduction; Research; Research Personnel; Resources; Rupture; Serum; Source; System; Testing; United States National Institutes of Health; egg; granulosa cell; novel; prevent; reproductive; response

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 尽管会产生性类固醇激素，但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配子、卵母细胞或卵子。 该功能是通过排卵过程实现的，其中完全发育的卵泡响应排卵促性腺激素激增的作用而破裂，并释放卵丘-卵母细胞复合物以进入生殖道并可能受精。 然而，卵泡破裂以及卵丘-卵母细胞复合物与卵泡内（颗粒）细胞层的分离需要通过复杂的蛋白酶系统进行显着的细胞重组和细胞外基质重塑。 在脱离之前，细胞与细胞接触的丧失以及卵丘细胞之间富含透明质酸的细胞外基质的形成，导致卵丘-卵母细胞复合物的大量增加或“膨胀”。 此外，来自非灵长类物种的最新数据表明，卵丘卵母细胞扩张（C-OE）涉及卵母细胞、颗粒/卵丘和血清衍生因子之间复杂的相互作用，因此关键成分的有针对性的破坏会损害排卵和受精。 这些发现与新概念一致，即可以选择性抑制卵泡蛋白水解、C-OE、卵母细胞释放，从而抑制生育力，而不改变女性生殖的其他方面，包括卵巢/月经周期。 因此，该项目的目的是检验蛋白酶、卵母细胞和颗粒/卵丘衍生蛋白控制灵长类动物卵泡破裂和 C-OE 的假设。 此外，还将确定阻断其合成或作用是否会阻止旧大陆（猕猴）猴的及时 C-OE、卵母细胞释放和妊娠。