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Molecular Biology of the Oocyte

卵母细胞的分子生物学

基本信息

批准号：
7967166
负责人：
JURRIEN DEAN
金额：
$ 216.46万
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7967166
关键词：
Adult Affect Animal Model Area BHLH Protein Biocompatible Materials Cell Adhesion Molecules Cell Lineage Cells Childhood Complement Complex Congenital Abnormality Contraceptive methods DNA Development Disease Embryo Embryonic Development Ethics Event Female Fertilization Gene Transfer Techniques Genes Genome Germ Germ Cells Growth Factor Herpes zoster disease Human Human Development Inner Cell Mass Investigation Mammalian Oviducts Mammals Mediating Molecular Molecular Biology Molecular Models Morula Mus Oocytes Oogenesis Organelles Ovarian Ovary Population Growth Process Proteins Public Health Reproductive Technology Somatic Cell Specificity Staging Taxon Zona Pellucida base egg embryo stage 2 extracellular folliculogenesis insight macromolecule male molecular modeling mouse development mouse model novel preimplantation prevent sperm cell success transcription factor zygote

项目摘要

Folliculogenesis: Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ-cell specific, basic helix-loop-helix transcription factor, FIGLA (Factor In the GermLine, Alpha). FIGLA is first detected at embryonic day 13.5 (E13.5) and persists in adult female mice. Initially investigated as an activator of female genes, it also represses male germline genes to prevent inappropriate expression during oogenesis. Current studies have identified potential oocyte-specific targets of FIGLA important for: 1) folliculogenesis; 2) fertilization; and 3) pre-implantation development. Fertilization: The specificity of sperm-egg recognition in mammals is mediated primarily by the zona pellucida. However, despite extensive investigation, there is no unifying model for the molecular basis of sperm interactions with the zona matrix that result in mammalian fertilization. Current studies investigate: 1) the molecular biology of the formation of the extracellular zona pellucida; 2) the molecular requirements of the zona pellucida matrix to support taxon-specific sperm-egg recognition; and 3) the mechanism by which post-fertilization polyspermy is prevented. Early Development: Activation of the embryonic genome in mice begins late in the one-cell zygote and is fully underway by the two-cell cleavage stage. Initial cell lineages that presage the inner cell mass and extra-embryonic trophectoderm are established when eight blastomeres compact to form polarized morulae in pre-implantation mouse development. In simpler model organisms, there is compelling evidence that persistent gene products from the egg are required for successful embryogenesis. However, in mice such effects have been documented only more recently and constitute a rapidly evolving area of investigation. Current studies investigate: 1) novel maternal effect genes that affect early mouse development; 2) components of a recently described maternally encoded subcortical complex; and 3) mechanisms by which the loss of the complex affects cleavage stage embryogenesis.

卵泡发生：哺乳动物的卵巢卵泡发生是一个复杂的过程，涉及生殖细胞和体细胞之间的相互作用。成功需要精心策划转录因子、细胞粘附分子和生长因子的表达。我们已经鉴定了一种生殖细胞特异性的基本螺旋-环-螺旋转录因子，FIGLA（生殖系因子，Alpha）。 FigLA 在胚胎第 13.5 天 (E13.5) 首次被检测到，并在成年雌性小鼠中持续存在。最初作为雌性基因的激活剂进行研究，它还抑制雄性种系基因以防止卵子发生过程中的不当表达。目前的研究已经确定了 FIFALA 潜在的卵母细胞特异性靶点，这些靶点对于以下方面很重要：1）卵泡发生； 2）施肥； 3）植入前发育。受精：哺乳动物精卵识别的特异性主要由透明带介导。然而，尽管进行了广泛的研究，但对于导致哺乳动物受精的精子与透明带基质相互作用的分子基础还没有统一的模型。目前的研究调查：1）细胞外透明带形成的分子生物学； 2) 透明带基质支持类群特异性精卵识别的分子要求； 3) 预防受精后多受精的机制。早期发育：小鼠胚胎基因组的激活在单细胞受精卵后期开始，并在两细胞分裂阶段完全开始。在小鼠植入前发育过程中，当八个卵裂球压缩形成极化桑葚胚时，预示着内细胞团和胚胎外滋养外胚层的初始细胞谱系就建立了。在更简单的模型生物体中，有令人信服的证据表明，成功的胚胎发生需要来自卵子的持久基因产物。然而，在小鼠中，这种效应直到最近才被记录下来，并且构成了一个快速发展的研究领域。目前的研究调查：1）影响小鼠早期发育的新型母体效应基因； 2）最近描述的母体编码皮质下复合体的组成部分； 3) 复合物的丢失影响卵裂期胚胎发生的机制。