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

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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.