Elimination of oocytes with asynapses during meiotic prophase progression in the mouse

在小鼠减数分裂前期过程中通过无突触消除卵母细胞

• 批准号: 203675-2012
• 负责人: TaketoHosotani, Teruko
• 金额: $ 2.04万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=546387
• 关键词: Elimination; oocytes; asynapses; during; meiotic

Meiosis is a fundamental process that generates haploid gametes for sexual reproduction in a wide range of species. However, the timing and regulatory mechanisms of meiotic progression differ considerably not only between species but also between the two sexes of mammals. A critical meiotic event is the pairing and recombination of paternal and maternal homologous chromosomes during the first meiotic prophase. This event is essential for securing proper segregation of homologous chromosomes at meiotic divisions as well as for generating genetic diversity in the offspring. Defects in meiotic recombination can result in aneuploidy, a major cause of embryonic death. To avoid such deleterious outcomes, a surveillance system operates to eliminate the germ cells with meiotic errors, but in different fashions between the two sexes; a failure in meiotic recombination invariably leads to a block of spermatogenesis but not necessarily to a block of oogenesis. Nevertheless, more than half of the initial population of female meiotic cells (oocytes) is eliminated during this period. Studies of female meiosis are technically challenging since germ cells enter meiosis and go through the meiotic prophase during fetal development. Nonetheless, it is imperative to clarify the female specific meiotic mechanisms in order to fully understand mammalian gametogenesis. My long-term objective is to understand the regulatory mechanisms of the meiotic progression in the mouse ovary. My short-term objective in the next five years is to test the hypothesis that a failure in chromosome pairing and recombination causes the silencing of their encoded genes and shift the balance between the apoptotic (programmed cell death) pathway and its endogenous inhibitors toward the elimination of the oocytes with meiotic errors. The results of the proposed study will give us an insight into the regulation of the meiotic progression and the nature of the surviving oocytes in mammalian females.

减数分裂是一个基本过程，在广泛的物种中产生单倍配子进行有性繁殖。然而，减数分裂进程的时机和调节机制不仅在物种之间，而且在两种哺乳动物之间也有很大差异。一个关键的减数分裂事件是第一个减数分裂预言期间父亲和母体同源染色体的配对和重组。该事件对于确保对减数分裂分裂的同源染色体的适当分离以及在后代产生遗传多样性至关重要。减数分裂重组的缺陷可能导致非整倍性，这是胚胎死亡的主要原因。为了避免这种有害的结果，监视系统可以运行以减数分裂错误的形状，但在两个性别之间的不同时尚中。减数分裂重组的失败总是导致精子发生的一块，但不一定会导致卵子发生。然而，在此期间，消除了女性减数分裂细胞（卵母细胞）的初始种群的一半以上。女性减数分裂的研究在技术上具有挑战性，因为生殖细胞进入减数分裂并经过胎儿发育过程中的减数分裂预言。但是，必须阐明女性特定的减数分裂机制，以充分了解哺乳动物的配子发生。我的长期目标是了解小鼠卵巢中减数分裂进程的调节机制。我在未来五年内的短期目标是测试以下假设：染色体配对和重组的失败会导致其编码基因的沉默，并将凋亡（程序性细胞死亡）途径之间的平衡及其内源性抑制剂之间的平衡转移到消除卵母细胞的情况下。拟议研究的结果将使我们深入了解减数分裂进程的调节以及哺乳动物女性中存活的卵母细胞的性质。