Signaling mechanisms that regulate meiosis in mammalian oocytes
调节哺乳动物卵母细胞减数分裂的信号机制
基本信息
- 批准号:7616729
- 负责人:
- 金额:$ 25.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-08-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:AKT Signaling PathwayAddressAdenylate CyclaseAffectAreaArrestinsBasic ScienceCell membraneCellsClinicClinicalCollaborationsCyclic AMPDevelopmentDown-RegulationEventFertilityFertilization in VitroFigs - dietaryG-Protein-Coupled ReceptorsGTP-Binding ProteinsGap JunctionsGoalsHumanHydrolysisIn VitroLeadLigandsLuteinizing HormoneMaintenanceMammalsMediatingMeiosisMeiotic Prophase IMethodsMicroinjectionsMusOocytesOvaryPathway interactionsPhosphotransferasesPhysiologicalPituitary GlandProcessProductionProteinsProto-Oncogene Proteins c-aktRGS ProteinsRGS2 geneRegulationReproductive BiologyReproductive PhysiologyResearchResearch PersonnelRodentRodent ModelSignal PathwaySignal TransductionStagingTechniquesWomanWomen&aposs HealthWorkbasedesensitizationeggfallsimprovedinterestoocyte maturationphosphoric diester hydrolaseprogramsresponse
项目摘要
DESCRIPTION (provided by applicant): The goal of this research is to examine the signaling events regulating meiotic progression in mammalian oocytes. Immature oocytes are arrested at prophase I, and in response to a surge of luteinizing hormone LH) that acts on the follicle cells, they re-enter meiosis and mature into eggs. The mechanism(s) by which LH transmits its signal from the follicle cells to the oocyte is not known. Aim 1 of this proposal will examine signaling mechanisms by which LH initiates meiotic resumption in mouse oocytes. Prior to the LH surge, meiotic arrest requires a high level of cAMP in the oocyte; this cAMP is produced by the G-protein coupled receptor GPRS, in the oocyte plasma membrane, that stimulates Gs to activate adenylate cyclase. In response to LH, cAMP levels in the oocyte fall, leading to meiotic resumption. Potential targets in the oocyte by which LH could act include the following: 1) GPR3, which could be turned off through the activation of G- protein receptor kinases (GRKs) and li-arrestins, a common mechanism for downregulating most GPCRs. 2) Gs, the activity of which could be inhibited by a regulator of G-protein signalling (RGS) protein. 3) The AKT/PKB signalling pathway, which has been shown to affect meiotic resumption in a variety of species. 4) Regulation at the level of gap junctions. These pathways will be investigated using recently developed methods for microinjecting follicle-enclosed oocytes. Aim 2 will examine if meiotic arrest and resumption in human oocytes depend on the same pathways as in rodent oocyte, by examining if human oocytes contain the same components of these signalling pathways. Aim 2 will also characterize cytoplasmic events that normally occur during human oocyte maturation. These studies will provide valuable information about which aspects of rodent models can be applied to human oocytes. The question of how meiosis is regulated is highly relevant to issues of women's health. In particular, it is of high interest clinically to develop methods for successfully maturing immature human oocytes in vitro, which could lead to improvements in in vitro fertilization treatments, as well as provide more options than are currently available for women to preserve their fertility. Improvements in in vitro maturation will require an understanding of all stages of meiotic arrest and the physiological mechanisms regulating the initiation of oocyte maturation. The proposed studies will contribute to the basic science background that underlies such clinical advances.
描述(由申请人提供):这项研究的目的是检查调节哺乳动物卵母细胞减数分裂进程的信号传导事件。未成熟的卵母细胞在预言I上被捕,并响应起作用卵泡细胞的黄体生成激素LH),它们重新进入减数分裂并成熟为卵。 LH将其信号从卵泡细胞传输到卵母细胞的机制尚不清楚。该提案的目标1将检查LH在小鼠卵母细胞中启动减数分裂恢复的信号传导机制。在LH激增之前,减数分裂逮捕需要在卵母细胞中高水平的营地。该营地是由卵母细胞质膜中的G蛋白偶联受体GPRS产生的,该受体GPR刺激GS激活腺苷酸循环酶。为了响应LH,卵母细胞的cAMP水平降落,导致减数分裂恢复。 LH可以起作用的卵母细胞中的潜在靶标包括以下内容:1)GPR3,可以通过激活G-蛋白受体激酶(GRKS)和Li-arrestins的激活来关闭GPR3,这是下调大多数GPCR的常见机制。 2)GS,其活性可以被G蛋白信号(RGS)蛋白的调节剂抑制。 3)AKT/PKB信号通路,已显示出会影响各种物种中的减数分裂恢复。 4)在间隙连接级别的调节。这些途径将使用最近开发的微型注射卵泡封闭的卵母细胞的方法进行研究。 AIM 2通过检查人类卵母细胞是否包含这些信号传导途径的相同成分,检查了人类卵母细胞中的减数分裂停滞和恢复是否取决于与啮齿动物卵母细胞相同的途径。 AIM 2还将表征通常在人类卵母细胞成熟过程中发生的细胞质事件。这些研究将提供有关啮齿动物模型的哪些方面可以应用于人类卵母细胞的宝贵信息。减数分裂的调节问题与妇女健康问题高度相关。特别是,在临床上开发成功成熟的未成熟人类卵母细胞的方法在临床上具有很高的兴趣,这可能会导致体外受精治疗的改善,并提供比目前可用于保持生育能力的更多选择。体外成熟的改善将需要了解减数分裂停滞的所有阶段以及调节卵母细胞成熟开始的生理机制。拟议的研究将有助于基础科学背景,这些基础科学背景是临床进展的基础。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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LISA M MEHLMANN其他文献
LISA M MEHLMANN的其他文献
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{{ truncateString('LISA M MEHLMANN', 18)}}的其他基金
Generation and characterization of a TRIM21 overexpressing mouse line
TRIM21 过表达小鼠系的生成和表征
- 批准号:
9807181 - 财政年份:2019
- 资助金额:
$ 25.9万 - 项目类别:
Signaling mechanisms that regulate meiosis in mammalian oocytes
调节哺乳动物卵母细胞减数分裂的信号机制
- 批准号:
7478706 - 财政年份:2007
- 资助金额:
$ 25.9万 - 项目类别:
Signaling mechanisms that regulate meiosis in mammalian oocytes
调节哺乳动物卵母细胞减数分裂的信号机制
- 批准号:
8109938 - 财政年份:2007
- 资助金额:
$ 25.9万 - 项目类别:
Signaling mechanisms that regulate meiosis in mammalian oocytes
调节哺乳动物卵母细胞减数分裂的信号机制
- 批准号:
7301264 - 财政年份:2007
- 资助金额:
$ 25.9万 - 项目类别:
Signaling mechanisms that regulate meiosis in mammalian oocytes
调节哺乳动物卵母细胞减数分裂的信号机制
- 批准号:
7810563 - 财政年份:2007
- 资助金额:
$ 25.9万 - 项目类别:
Regulation of Meiotic Arrest in Oocytes by G-Proteins
G 蛋白对卵母细胞减数分裂停滞的调节
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6758536 - 财政年份:2003
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$ 25.9万 - 项目类别:
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