细胞周期蛋白 D-CDK4/CDK6 和细胞周期蛋白 E-CDK2 通路的时空调变：对免疫型不明原因复发性自然流产小鼠模型中蜕膜化不足机制的影响。
Temporal changes in cyclinD-CDK4/CDK6 and cyclinE-CDK2 pathways: implications for the mechanism of deficient decidualization in an immune-based mouse model of unexplained recurrent spontaneous abortion.
机构信息
Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
出版信息
Mol Med. 2022 Sep 1;28(1):100. doi: 10.1186/s10020-022-00523-3.
BACKGROUND
Deficient endometrial decidualization has been associated with URSA. However, the underlying mechanism is poorly understood. This study aimed to investigate the temporal cytokine changes and the involvement of CyclinD-CDK4/6 and CyclinE-CDK2 pathways in the regulation of the G1 phase of the cell cycle during decidualization in a murine model of URSA.
METHODS
Serum and decidual tissues of mice were collected from GD4 to GD8. The embryo resorption and abortion rates were observed on GD8 and the decidual tissue status was assessed. In addition, PRL, Cyclin D, CDK6, CDK4, Cyclin E, CDK2 expression in mice were measured.
RESULTS
URSA mice showed high embryo resorption rate and PRL, Cyclin D, Cyclin E CDK2, CDK4, CDK6 down-regulation during decidualization. The hyperactivated Cyclin D-CDK4/CDK6 and cyclin E/CDK2 pathways inhibit the decidualization process and leading to deficient decidualization.
CONCLUSION
Insufficient decidualization is an important mechanism of URSA. which is related to the decrease of Cyclin D、Cyclin E、 CDK2、CDK4 and CDK6 in decidualization process of URSA.
背景
子宫内膜蜕膜化不足与 URSA 有关。然而，其潜在机制尚不清楚。本研究旨在探讨细胞周期 G1 期调控中细胞因子的时空调控变化以及细胞周期蛋白 D-CDK4/6 和细胞周期蛋白 E-CDK2 途径在 URSA 小鼠模型蜕膜化过程中的参与情况。
方法
从 GD4 到 GD8 收集小鼠血清和蜕膜组织。观察 GD8 时的胚胎吸收率和流产率，并评估蜕膜组织状态。此外，还测量了小鼠中的 PRL、Cyclin D、CDK6、CDK4、Cyclin E、CDK2 的表达。
结果
URSA 小鼠在蜕膜化过程中表现出高胚胎吸收率和 PRL、Cyclin D、Cyclin E、CDK2、CDK4、CDK6 的下调。过度激活的 Cyclin D-CDK4/CDK6 和 cyclin E/CDK2 途径抑制了蜕膜化过程，导致蜕膜化不足。
结论
蜕膜化不足是 URSA 的一个重要机制，与 URSA 蜕膜化过程中 Cyclin D、Cyclin E、CDK2、CDK4 和 CDK6 的减少有关。
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