Consistency and synchronization of AMPK-glycogen in endometrial epithelial cells are critical to the embryo implantation

in Reproduction
Authors:
Li Nie Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Li-xue Zhang Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Yi-cheng Wang Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Yun Long Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Yong-dan Ma Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Lin-chuan Liao West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China

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Xin-hua Dai West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China

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Zhi-hui Cui Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Huan Liu Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Zhao-qi Wang Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Zi-yang Ma Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Dong-zhi Yuan Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

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Li-min Yue Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China
Reproductive Endocrinology and Regulation Joint Laboratory, West China Second Hospital, Sichuan University, Chengdu, China

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Correspondence should be addressed to D Yuan or L Yue; Email: yuandongzhi@scu.edu.cn or yuelimin@scu.edu.cn
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Uterine receptivity to the embryo is crucial for successful implantation. The establishment of uterine receptivity requires a large amount of energy, and abnormal energy regulation causes implantation failure. Glucose metabolism in the endometrium is tissue specific. Glucose is largely stored in the form of glycogen, which is the main energy source for the endometrium. AMP-activated protein kinase (AMPK), an important energy-sensing molecule, is a key player in the regulation of glucose metabolism and its regulation is also tissue specific. However, the mechanism of energy regulation in the endometrium for the establishment of uterine receptivity remains to be elucidated. In this study, we aimed to investigate the energy regulation mechanism of mouse uterine receptivity and its significance in embryo implantation. The results showed that the AMPK, p-AMPK, glycogen synthase 1, and glycogen phosphorylase M levels and the glycogen content in mouse endometrial epithelium varied in a periodic manner under regulation by the ovarian hormone. Specifically, progesterone significantly activated AMPK, promoted glycogenolysis, and upregulated glycogen phosphorylase M expression. AMPK regulated glycogen phosphorylase M expression and promoted glycogenolysis. AMPK was also found to be activated by changes in the energy or glycogen of the endometrial epithelial cells. The inhibition of AMPK activity or glycogenolysis altered the uterine receptivity markers during the window of implantation and ultimately interfered with implantation. In summary, consistency and synchronization of AMPK and glycogen metabolism constitute the core regulatory mechanism in mouse endometrial epithelial cells involved in the establishment of uterine receptivity.

 

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