卵子排卵前老化导致的染色体非整倍性是高龄女性妊娠失败的主要原因之一，但其分子机制尚未明确。在前期工作中，我们发现哺乳动物特有的皮层下母源复合体SCMC核心组分Mater在小鼠老化卵子中明显下降。在小鼠中敲除Mater会导致SCMC其他已知组分的缺失和2-cell发育阻滞。实验发现Mater敲除卵子产生严重的染色体非整倍性，这表明SCMC/Mater对于维持卵子染色体整倍性是必须的，但机制尚待研究。值得注意的是，SCMC缺失会导致微管稳定性降低，这可能与染色体非整倍性有关。本项目拟以Mater敲除小鼠以及小鼠和人的老化卵子为模型，利用显微注射、免疫荧光、活细胞实时成像等研究手段，探究SCMC缺失导致的微管不稳定是否通过影响纺锤体组装，进而导致染色体非整倍性发生。本项目的顺利开展有助于深入理解减数分裂过程中染色体精确遗传的分子机制，为临床上卵子老化相关问题的研究提供理论基础。

Chromosomal aneuploidy in preovulatory aging egg is one of the main reasons for pregnancy failure of women with advanced age. However, the molecular mechanism is still unclear. In preliminary experiments, we find that Mater, a core component of subcortial maternal complex (SCMC), significantly decreases in mice aging eggs. Depletion of maternal Mater leads to deficiency of other SCMC components (Tle6, Floped, Zbed3 and Filia) and 2-cell arrest in mice. We also find that the chromosomal aneuploidy in Mater null eggs is more severe than that in normal. The results indicate that SCMC with Mater as core is essential for maintaining chromosomal euploidy in oocyte. However, how it works remains largely uncharacterized. In addition, loss of SCMC induces decrease of acetylated a-tubulin, a microtubule stability marker which is potentially related to euploidy. In this project, utilizing reproductive technologies including microinjection, immunofluorescence and time-lapse imaging in Mater null mouse and aging oocytes from mouse or human, we attempt to prove the hypothesis that the unstable microtubules induced by deficiency of SCMC bring about chromosomal aneuploidy via disrupting spindle assembly in meiosis. The implementation of the project contributes to deep understanding about the molecular mechanism of precise inheritance of chromosomes during meiosis, and provides theoretical basis for studying oocyte aging in clinic.