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首页> 外文期刊>Cell cycle >Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice
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Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice

机译：细胞内pH升高会出现在老年卵母细胞中，并导致与小鼠内聚力丧失相关的卵母细胞非整倍性

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Increases in the aneuploidy rate caused by the deterioration of cohesion with increasing maternal age have been well documented. However, the molecular mechanism for the loss of cohesion in aged oocytes remains unknown. In this study, we found that intracellular pH (pH(i)) was elevated in aged oocytes, which might disturb the structure of the cohesin ring to induce aneuploidy. We observed for the first time that full-grown germinal vesicle (GV) oocytes displayed an increase in pH(i) with advancing age in CD1 mice. Furthermore, during the in vitro oocyte maturation process, the pH(i) was maintained at a high level, up to approximate to 7.6, in 12-month-old mice. Normal pH(i) is necessary to maintain protein localization and function. Thus, we put forward a hypothesis that the elevated oocyte pH(i) might be related to the loss of cohesion and the increased aneuploidy in aged mice. Through the in vitro alkalinization treatment of young oocytes, we observed that the increased pH(i) caused an increase in the aneuploidy rate and the sister inter-kinetochore (iKT) distance associated with the strength of cohesion and caused a decline in the cohesin subunit SMC3 protein level. Young oocytes with elevated pH(i) exhibited substantially the increase in chromosome misalignment.
机译：有证据表明，随着产妇年龄的增长，内聚力降低导致非整倍体率增加。然而，衰老的卵母细胞内聚力丧失的分子机制仍然未知。在这项研究中，我们发现衰老的卵母细胞中的细胞内pH（pH（i））升高，这可能会干扰粘附素环的结构以诱导非整倍性。我们首次观察到，成年的胚泡（GV）卵母细胞在CD1小鼠中随着年龄的增长而显示出pH（i）的增加。此外，在体外卵母细胞成熟过程中，在12个月大的小鼠中，pH（i）维持在很高的水平，直至大约7.6。正常pH（i）是维持蛋白质定位和功能所必需的。因此，我们提出了一个假设，即卵母细胞pH（i）升高可能与衰老小鼠的内聚力丧失和非整倍性增加有关。通过对年轻卵母细胞的体外碱化处理，我们观察到pH（i）的增加导致非整倍体率的增加以及与内聚力相关的姐妹动粒间距离（iKT）的增加，并导致内粘蛋白亚基的下降SMC3蛋白水平。 pH（i）升高的年轻卵母细胞显着增加染色体错位。

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