MECHANISMS OF MAMMALIAN OOCYTE MATURATION

说明(改编自调查员摘要)：目标 本研究旨在了解细胞间和细胞内的信号转导。 触发哺乳动物卵母细胞成熟的机制。完全成熟 卵巢中的卵母细胞被体积体和颗粒细胞包围， 形成卵泡。卵母细胞停滞在减数分裂前期I。 排卵前黄体生成素(LH)的激增导致卵母细胞 恢复减数分裂，这一过程被称为卵母细胞成熟。卵母细胞成熟 最终发育成成熟的卵子，从卵巢中释放出来 在排卵期间。黄体生成素启动恢复的机制 对于任何哺乳动物物种，减数分裂都不是完全了解的。环腺苷 一磷酸(CAMP)和钙似乎在启动过程中起作用 成熟；然而，钙参与的更确凿的证据 在触发卵母细胞成熟的过程中，需要。 对卵母细胞成熟的激素依赖调节将在 一种可以第一次检查变化的系统 卵母细胞及周围细胞内游离cAMP和钙 滤泡细胞。原始卵泡和腔前卵泡将从 未成熟大鼠的卵巢；当在培养中生长时，这些卵巢形成大的 与正常人的组织和生理相似的卵泡 毛囊。这种培养系统允许光学成像和细胞 活体卵泡内显微注射卵母细胞以了解黄体生成素是如何发挥其功能的 效果。将使用cAMP和钙的荧光探针来澄清 CAMP在卵母细胞成熟中的作用及钙是否起作用 作为这一过程中的信号媒介。类似的卵泡培养系统有 很可能在未来用来培养来自原始或 腔前卵泡。在这样的文化体系完善之前， 确定发育过程中的代谢和激素需求 颗粒细胞和卵母细胞很重要。这项研究的结果 将提供对以下信号机制的更好理解 从未成熟的卵母细胞产生成熟的卵子。

DESCRIPTION (Adapted from the Investigator's Abstract): The objective of this research is to understand the intercellular and intracellular signaling mechanisms that trigger maturation of the mammalian oocyte. Fully grown oocytes in the ovary are surrounded by somatic cumulus and granulosa cells, which form the follicle. Oocytes are arrested in prophase I of meiosis. The preovulatory surge of luteinizing hormone (LH) causes the oocyte to resume meiosis, a process known as oocyte maturation. Oocyte maturation culminates in development of a mature egg that is released from the ovary during ovulation. The mechanism by which LH initiates the resumption of meiosis is not fully understood for any mammalian species. Cyclic adenosine monophosphate (cAMP) and calcium appear to have roles in initiating maturation; however, more definitive evidence for participation of calcium in triggering oocyte maturation is needed. Hormone dependent regulation of oocyte maturation will be studied in a system in which it is possible, for the first time, to examine the changes in intracellular free cAMP and calcium in the oocyte and surrounding follicular cells. Primordial and preantral follicles will be isolated from the ovaries of immature rats; when grow in culture, these form large follicles that closely mimic the organization and physiology of the normal follicle. This culture system permits optical imaging and cellular microinjection of oocytes in living follicles to learn how LH exerts its effects. Fluorescent probes for cAMP and calcium will be used to clarify the role of cAMP in oocyte maturation and to determine if calcium functions as a signaling agent in the process. Similar follicle culture systems are likely to be used in the future to culture human oocytes from primordial or preantral ovarian follicles. Before such culture systems are perfected, defining the metabolic and hormonal requirements for development of the granulosa cells and oocyte is important. The results from this research will provide a greater understanding of the signaling mechanisms that produce a mature egg from an immature oocyte.