Cell Surface Changes During the Egg-to-Embryo Transition

卵子到胚胎转变过程中细胞表面的变化

• 批准号: 7595737
• 负责人: GARY M WESSEL
• 金额: $ 25.38万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7595737
• 关键词: Animals; Biochemical; Calcium Binding; Cell Surface Proteins; Cell membrane; Cell surface; Cells; Cleaved cell; Clinical; Cytoplasmic Granules; Cytoplasmic Protein; Development; Embryo; Endocytosis; Enzyme Activation; Enzymes; Excision; Fertilization; Gene Expression; Genetic Transcription; Genomics; Germ Cells; Hour; Human; Hydrogen Peroxide; Insemination; Lead; Learning; Lipids; Mammals; Maternal Messenger RNA; Membrane Proteins; Methods; Molecular; Mutate; N-terminal; Oocytes; Outcome Study; Oxidases; Peptide Hydrolases; Population; Process; Production; Proteins; Regulation; Reproductive Health; Research; Resources; Sea Urchins; Serine Protease; Serpins; Signal Transduction; Starfish; Strongylocentrotus purpuratus; Testing; Vertebrates; base; egg; genome sequencing; programs; protein function; public health relevance; reproductive; research study; sperm cell

DESCRIPTION (provided by applicant): If fertilized, all eggs undergo an egg-to-embryo transition. Within minutes or hours of insemination, depending on the animal, the egg shuffles its existing molecular machinery and transforms itself into a cell with vastly different developmental potential. The first mechanistic alteration of this egg-to-embryo transition establishes the block to polyspermy, which is followed by and integrated with the turnover of maternal mRNA and cytoplasmic proteins, altered signal transduction capabilities, and changes at the cell surface including the addition and removal of specific membrane proteins and lipids. This transition is independent of new transcriptional activity, and for technical reasons, a majority of recent research towards understanding the egg-to-embryo transition has focused on signal transduction mechanisms and changes in mRNAs. The sea urchin and starfish, however, offer an opportunity to examine the changes that occur specifically at the cell surface. While the details of this process differ among animals, as with much of the reproductive phenomena, all eggs undergo this general transition. We will take advantage of the sea urchin and starfish because 1) millions of oocytes, eggs and embryos are readily obtained; 2) all the major proteins of the cortical granules have been defined; 3) the egg and oocyte plasma membrane can be manipulated experimentally in many ways; and 4) the genome sequence and genomic resources from the sea urchin Strongylocentrotus purpuratus are available. Results of this study will elucidate conserved mechanisms of this major developmental transition in all animals. Furthermore, because the changes examined here are at the cell surface, they will help clinicians develop new methods to non-invasively assess developmental potential in IVF applications for humans. PUBLIC HEALTH RELEVANCE: Immediately after fertilization, the egg rapidly transforms into an embryo with many new biochemical, cellular, and developmental features. This essential change is programmed into the egg and is independent of new gene expression; i.e., they reflect changes of the existing molecular machinery. Our research focuses on the changes that occur on the cell surface of the egg to embryo transition. These are some of the most rapid and conserved changes that occur in embryos and are detectable from the outside of the cell. Thus, this research will lead to a better understanding of a major transition in fertilization and development of all animals, and to the identification of non invasive, early markers indicative of successful development. Our results will have particular significance to clinical IVF predictions in human reproductive health.

描述（由申请人提供）：如果受精，则所有卵都会发生卵到胚胎过渡。在数分钟或几个小时内，根据动物的不同，鸡蛋将其现有的分子机制散发出来，并将其自身转变为具有截然不同的发育潜力的细胞。该卵到embryo跃迁的第一个机理改变建立了对多体植物的块，然后与母体mRNA和细胞质蛋白的营业额相结合，并整合了信号转导能力，并改变了细胞表面的变化，包括添加和去除特定膜蛋白和脂肪。这种过渡与新的转录活性无关，出于技术原因，最近大多数研究旨在理解鸡蛋到embryo的过渡都集中在信号转导机制和mRNA的变化上。但是，海胆和海星提供了一个机会，可以检查专门在细胞表面发生的变化。尽管动物的细节在动物之间有所不同，就像许多生殖现象一样，所有卵都经历了这种一般过渡。我们将利用海胆和海星，因为1）很容易获得数百万卵母细胞，卵和胚胎； 2）已经定义了皮质颗粒的所有主要蛋白质； 3）卵和卵母细胞质膜可以通过多种方式进行实验操纵； 4）可提供来自海胆strongyylocentrotus紫pura的基因组序列和基因组资源。这项研究的结果将阐明所有动物中这种主要发育过渡的保守机制。此外，由于此处检查的变化位于细胞表面，因此它们将帮助临床医生开发新方法，以非侵入性评估人类IVF应用中的发育潜力。公共卫生相关性：受精后，卵立即迅速转化为具有许多新的生化，细胞和发育特征的胚胎。这种基本变化被编程到卵中，与新基因表达无关。即，它们反映了现有分子机械的变化。我们的研究重点是卵子表面上发生的变化到胚胎过渡。这些是胚胎中发生的一些最快，最保守的变化，可从细胞的外部检测到。因此，这项研究将使人们对所有动物的受精和发育的重大过渡，以及鉴定非侵入性的，早期的标志物，这表明成功发展。我们的结果将对人类生殖健康中的临床IVF预测具有特殊意义。