Studies suggested that postovulatory oocyte aging might be prevented by maintaining a high maturation-promoting factor (MPF) activity. Whether AMP-activated protein kinase (AMPK) plays any role in postovulatory oocyte aging is unknown. Furthermore, while activation of AMPK stimulates meiotic resumption in mouse oocytes, it inhibits meiotic resumption in pig and bovine oocytes. Thus, the species difference in AMPK regulation of oocyte MPF activities is worth in-depth studies. This study showed that AMPK activation with metformin or AICAR and inactivation with compound C significantly increased and decreased, respectively, the activation susceptibility (AS) and other aging parameters in aging mouse oocytes. While AMPK activity increased, MPF activity and cAMP decreased significantly with time post ovulation. In vitro activation and inactivation of AMPK significantly decreased and increased the MPF activity, respectively. MPF upregulation with MG132 or downregulation with roscovitine completely abolished the effects of AMPK activation or inactivation on AS of aging oocytes, respectively. AMPK facilitated oocyte aging with increased reactive oxygen species (ROS) and cytoplasmic calcium. Furthermore, treatment with Ca²⁺/calmodulin-dependent protein kinase (CaMK) inhibitors significantly decreased AS and AMPK activation. Taken together, the results suggested that AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium.

中文翻译：

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AMP 活化蛋白激酶在小鼠卵母细胞排卵后衰老过程中的作用†。

研究表明，通过维持高成熟促进因子 (MPF) 活性可以防止排卵后卵母细胞老化。AMP 活化蛋白激酶 (AMPK) 是否在排卵后卵母细胞衰老中起任何作用尚不清楚。此外，虽然 AMPK 的激活会刺激小鼠卵母细胞的减数分裂恢复，但它会抑制猪和牛卵母细胞的减数分裂恢复。因此，AMPK调节卵母细胞MPF活性的物种差异值得深入研究。该研究表明，二甲双胍或 AICAR 的 AMPK 激活和化合物 C 的失活分别显着增加和降低了衰老小鼠卵母细胞的激活易感性 (AS) 和其他衰老参数。虽然 AMPK 活性增加，但 MPF 活性和 cAMP 随排卵后时间显着降低。体外AMPK 的激活和失活分别显着降低和增加 MPF 活性。MG132 的 MPF 上调或 roscovitine 的下调完全消除了 AMPK 激活或失活对衰老卵母细胞 AS 的影响。AMPK 通过增加活性氧 (ROS) 和细胞质钙促进卵母细胞衰老。此外，用 Ca ²⁺ /钙调蛋白依赖性蛋白激酶 (CaMK) 抑制剂治疗显着降低 AS 和 AMPK 活化。综上所述，结果表明 AMPK 通过抑制 MPF 活性促进卵母细胞衰老，而排卵后卵母细胞衰老通过增加 ROS 和细胞质钙激活 CaMKs 来激活 AMPK，cAMP 降低。