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

减数分裂是一个基本的过程，产生单倍体配子的有性生殖在广泛的物种。然而，减数分裂进程的时间和调节机制不仅在物种之间而且在哺乳动物的两性之间存在很大差异。一个关键的减数分裂事件是在第一次减数分裂前期父源和母本同源染色体的配对和重组。这一事件对于确保减数分裂时同源染色体的正确分离以及后代中产生遗传多样性是必不可少的。减数分裂重组的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，一个监视系统的运作，以消除生殖细胞与减数分裂错误，但在不同的性别之间的方式;减数分裂重组失败总是导致精子发生的障碍，但不一定是卵子发生的障碍。然而，超过一半的初始群体的女性减数分裂细胞（卵母细胞）在此期间被淘汰。女性减数分裂的研究在技术上具有挑战性，因为生殖细胞在胎儿发育期间进入减数分裂并经历减数分裂前期。然而，为了全面了解哺乳动物配子发生，必须阐明雌性特有的减数分裂机制。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测试的假设，染色体配对和重组的失败导致其编码基因的沉默和转移之间的平衡的凋亡（程序性细胞死亡）途径和内源性抑制剂对消除卵母细胞减数分裂错误。本研究的结果将使我们对哺乳动物雌性卵母细胞减数分裂进程的调控和存活卵母细胞的性质有更深入的了解。

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.