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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569987
• 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.

减数分裂是产生单倍体配子进行有性生殖的一个基本过程。然而，减数分裂过程的时间和调控机制不仅在物种之间，而且在哺乳动物的两性之间也存在很大差异。一个关键的减数分裂事件是在第一次减数分裂前期父本和母本同源染色体的配对和重组。这一事件对于确保同源染色体在减数分裂时的适当分离以及后代遗传多样性的产生至关重要。减数分裂重组缺陷可导致非整倍体，这是胚胎死亡的主要原因。为了避免这种有害的结果，一个监视系统运作，以消除有减数分裂错误的生殖细胞，但在两性之间以不同的方式；减数分裂重组失败总是会导致精子发生障碍，但不一定会导致卵子发生障碍。然而，在此期间，超过一半的初始雌性减数分裂细胞（卵母细胞）被消除。研究女性减数分裂在技术上具有挑战性，因为生殖细胞在胎儿发育过程中进入减数分裂并经历减数分裂前期。尽管如此，为了充分了解哺乳动物配子发生，明确雌性特定的减数分裂机制是必要的。我的长期目标是了解小鼠卵巢减数分裂进程的调控机制。我在未来五年的短期目标是验证染色体配对和重组失败导致其编码基因沉默的假设，并改变凋亡（程序性细胞死亡）途径及其内源性抑制剂之间的平衡，以消除具有减数分裂错误的卵母细胞。本研究的结果将使我们对哺乳动物雌性减数分裂过程的调控和存活卵母细胞的性质有更深入的了解。