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：
7933171
负责人：
JANICE P EVANS
金额：
$ 2.55万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2010-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7933171
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 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 Ovum Parthenogenesis Pathway interactions Pattern 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 insight member membrane model moesin prevent programs radixin protein receptor 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）：据信，多工或卵子受精于1个以上的精子，是人类自发怀孕至少5％的原因。为了抑制其他精子的施肥，卵已经开发了预防性机制，称为多植物的块。鸡蛋额外细胞涂层水平的块在许多不同的动物物种中都得到了很好的特征，并且在某些非哺乳动物物种中可以理解卵质膜水平的块。但是，尽管数据可以追溯到50 - 90年，但它提供了证据的证据，但实际上对哺乳动物卵中的多植物的膜块几乎一无所知。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在这种后有效性变化中涉及的2个成分，可将鸡蛋膜从支持施肥的形式转化为一种阻止其的形式。该项目的广泛长期目标是阐明膜块的机制到多物质的机理，从启动膜块建立的受精相关信号到卵膜和皮层的变化，以防止额外的受精。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，我们在该提案中的研究将解决以下特定目标。具体目标1将确定精子和精子诱导的Ca2+信号传导诱导膜块的建立的机制。该目标将确定膜块建立中涉及哪些精子成分，以及精子诱导的Ca2+信号如何影响膜块的特征。特定的目标2将通过识别涉及在膜块建立到polyspermy的Ca2+依赖性效应子分子来表征CA2+之后的下一步。最后，特定的目标3将集中在途径的后期步骤上，最终在膜块中沿膜块到多植物，从而检查了卵膜和皮质的特定变化。该目标将检验的假设是皮质颗粒胞吐作用，内吞作用和皮质组成和膜序列的施肥后变化有助于下调卵膜对精子的下调，后者是受精的。这些对精子诱导的信号，钙和施肥后膜和皮质动力学的探究将为哺乳动物膜块的细胞和分子机制提供重要的见解，从而促进了我们在生殖和发育生物学中对这个基本问题的了解。