Role of ataxia‐telangiectasia mutated (ATM) in porcine oocyte in vitro maturation
Role of ataxia‐telangiectasia mutated (ATM) in porcine oocyte in vitro maturation
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DOI：
10.1002/cbin.10439
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发表时间：
2015-06
影响因子：
3.9
通讯作者：
Z. Lin;Nam-Hyung Kim
中科院分区：
文献类型：
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作者：
Z. Lin;Nam-Hyung Kim
共济失调-毛细血管扩张突变（ATM）对于DNA损伤反应、细胞周期检查点和细胞凋亡至关重要。重要的努力集中在阐明ATM和其他核信号转导之间的关系，然而，很少有人知道ATM和卵母细胞减数分裂成熟之间的联系。本研究探讨了ATM在猪卵母细胞中的功能。ATM在卵母细胞成熟的各个阶段都有表达，主要定位于细胞核。此外，ATM特异性抑制剂KU-55933阻断了猪卵母细胞的成熟，降低了经历生殖囊泡破裂（GVBD）和第一极体排出的卵母细胞的百分比。KU-55933还降低了DNA损伤相关基因（乳腺癌1、不受苯并咪唑1抑制的出芽和P53）的表达，并降低了AKT和其他主要在G2/M期表达的细胞周期调控基因（包括骨形态发生蛋白15、生长分化因子9、细胞分裂周期蛋白2、细胞周期蛋白B1和AKT）的mRNA和蛋白水平。KU-55933处理降低了孤雌激活后囊胚的发育潜力，并增加了细胞凋亡水平。总之，这些数据表明，ATM影响猪卵母细胞的减数分裂和细胞质成熟，可能是通过降低它们对DNA链断裂的敏感性，刺激AKT途径，和/或改变其他母体基因的表达。
Ataxia‐telangiectasia mutated (ATM) is critical for the DNA damage response, cell cycle checkpoints, and apoptosis. Significant effort has focused on elucidating the relationship between ATM and other nuclear signal transducers; however, little is known about the connection between ATM and oocyte meiotic maturation. We investigated the function of ATM in porcine oocytes. ATM was expressed at all stages of oocyte maturation and localized predominantly in the nucleus. Furthermore, the ATM‐specific inhibitor KU‐55933 blocked porcine oocyte maturation, reducing the percentages of oocytes that underwent germinal vesicle breakdown (GVBD) and first polar body extrusion. KU‐55933 also decreased the expression of DNA damage‐related genes (breast cancer 1, budding uninhibited by benzimidazoles 1, and P53) and reduced the mRNA and protein levels of AKT and other cell cycle‐regulated genes that are predominantly expressed during G2/M phase, including bone morphogenetic protein 15, growth differentiation factor 9, cell division cycle protein 2, cyclinB1, and AKT. KU‐55933 treatment decreased the developmental potential of blastocysts following parthenogenetic activation and increased the level of apoptosis. Together, these data suggested that ATM influenced the meiotic and cytoplasmic maturation of porcine oocytes, potentially by decreasing their sensitivity to DNA strand breaks, stimulating the AKT pathway, and/or altering the expression of other maternal genes.