THE MEMBRANE BLOCK TO POLYSPERMY IN MAMMALIAN EGGS

哺乳动物卵子中多精受精的膜阻滞

基本信息

批准号：
7391829
负责人：
JANICE P EVANS
金额：
$ 25.53万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-20 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7391829
关键词：
1,2-diacylglycerol Accounting Actin-Binding Protein Actins Address Adhesions Affect Animals Annexins Back Binding CDC2 Protein Kinase Calcineurin Calcium Calcium Signaling Calmodulin Calpain Cell Adhesion Molecules Cell Cycle Cell Shape Cell membrane Characteristics Cleaved cell Condition Cyclin B Cytoplasmic Granules Cytoskeleton Data Development Developmental Biology Diglycerides Down-Regulation ERM protein Embryo Endocytosis Endoplasmic Reticulum Event Excision Exocytosis Extracellular Matrix Family Fertilization Fertilization in Vitro Figs - dietary Goals Gray unit of radiation dose Human Intracytoplasmic Sperm Injections Investigation Ionophores Kinetics Knowledge Lead Marine Invertebrates Mediating Membrane Membrane Proteins Modeling Molecular Mus Numbers Ovum Parthenogenesis Pathway interactions Pattern Personal Satisfaction Phosphatidylinositol 4,5-Diphosphate Phosphotransferases Polyploidy Pregnancy loss Principal Investigator Process Protein Family Protein Kinase C Proteins Publishing RNA Interference Research Personnel Retinal Cone Series Signal Pathway Signal Transduction Sperm Head Sperm-Ovum Interactions Surface Testing Text Time Vertebrates Work attenuation egg experience ezrin follow-up inhibitor/antagonist inositol-1,4,5-triphosphate receptor insight member membrane model moesin prevent programs radixin protein reproductive research study response sperm cell tool zygote

项目摘要

DESCRIPTION (provided by applicant): Polyspermy, or fertilization of an egg by more than 1 sperm, is believed to be the cause of at least 5% of spontaneous pregnancy loss in humans. To inhibit fertilization by additional sperm, eggs have developed preventative mechanisms known as blocks to polyspermy. The block at the level of the egg extra cellular coat has been well characterized in many different animal species, and the block at the level of the egg plasma membrane is understood in some non-mammalian species. However, virtually nothing is known about the membrane block to polyspermy in mammalian eggs, despite data dating back 50-90 years that provide evidence for its existence. Our recent data demonstrates that sperm-induced Ca2+ signaling and the egg actin cytoskeleton are 2 components involved in this post-fertilization change that transforms the egg membrane from a form that supports fertilization to 1 that prevents it. The broad, long-term goal of this project is elucidating the mechanism of the membrane block to polyspermy, from the fertilization-associated signaling that initiates membrane block establishment to the changes in the egg membrane and cortex that prevent additional fertilization. To make progress toward this goal and to build on our recent published and preliminary data, our studies in this proposal will address the following specific aims. Specific Aim 1 will determine the mechanisms by which sperm and sperm-induced Ca2+ signaling induce the establishment of the membrane block. This aim will identify what sperm component(s) is involved in membrane block establishment and how sperm-induced Ca2+ signaling affects characteristics of the membrane block. Specific Aim 2 will characterize the next step in the pathway following Ca2+ by identifying the Ca2+-dependent effector molecules that are involved in the establishment of the membrane block to polyspermy. Finally, Specific Aim 3 will focus on the later steps of the pathway culminating in the membrane block to polyspermy, examining specific changes in the egg membrane and cortex. This aim will test the hypotheses that cortical granule exocytosis, endocytosis, and post-fertilization changes in cortex composition and membrane order contribute to the down-regulation of egg membrane receptivity to sperm that follows fertilization. These inquiries into sperm-induced signaling, calcium, and post-fertilization membrane and cortical dynamics will provide important insights into the cellular and molecular mechanisms underlying the mammalian membrane block to polyspermy, advancing our knowledge of this fundamental question in reproductive and developmental biology.

描述（由申请人提供）：多精受精，即一个卵子被超过 1 个精子受精，被认为是导致人类至少 5% 自然妊娠流产的原因。为了抑制额外精子的受精，卵子形成了称为阻止多精受精的预防机制。在许多不同的动物物种中，卵细胞外衣层水平的阻断已得到很好的表征，并且在一些非哺乳动物物种中，卵质膜水平的阻断也得到了了解。然而，尽管 50-90 年前的数据提供了其存在的证据，但实际上我们对哺乳动物卵子中对多精受精的膜阻断一无所知。我们最近的数据表明，精子诱导的 Ca2+ 信号传导和卵子肌动蛋白细胞骨架是参与受精后变化的两个组成部分，该变化将卵膜从支持受精的形式转变为阻止受精的形式。该项目的广泛、长期目标是阐明膜阻滞与多精受精的机制，从启动膜阻滞建立的受精相关信号到阻止额外受精的卵膜和皮质变化。为了朝着这一目标取得进展并以我们最近发布的初步数据为基础，我们在本提案中的研究将解决以下具体目标。具体目标 1 将确定精子和精子诱导的 Ca2+ 信号传导诱导膜块建立的机制。这一目标将确定哪些精子成分参与膜块的建立以及精子诱导的 Ca2+ 信号如何影响膜块的特性。具体目标 2 将通过鉴定参与建立多精受精膜阻断的 Ca2+ 依赖性效应分子来表征 Ca2+ 途径的下一步。最后，具体目标 3 将重点关注最终实现膜阻滞到多精受精途径的后续步骤，检查卵膜和皮质的具体变化。该目标将检验以下假设：皮质颗粒胞吐作用、内吞作用以及受精后皮质组成和膜顺序的变化导致受精后卵膜对精子的接受性下调。这些对精子诱导的信号传导、钙以及受精后膜和皮质动力学的研究将为哺乳动物膜阻断多精受精的细胞和分子机制提供重要的见解，增进我们对生殖和发育生物学这一基本问题的了解。