Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway

Abstract Background We have previously found that the energy level in sows affects the activation of primordial follicles. Glucose is the primary metabolic substrate of dietary energy and its effect and mechanism of action with regards to the activation and development of primordial follicle remain...

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Main Authors: Shengyu Xu, Xiaoling Wu, Yanpeng Dong, Mengmeng Xu, Zimei Li, Sirun Chen, Yong Zhuo, Yan Lin, Lianqiang Che, Zhengfeng Fang, Bin Feng, Jian Li, Jianping Wang, De Wu, Zhihua Ren
Format: Article
Language:English
Published: Wiley 2020-07-01
Series:Clinical and Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/ctm2.122
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author Shengyu Xu
Xiaoling Wu
Yanpeng Dong
Mengmeng Xu
Zimei Li
Sirun Chen
Yong Zhuo
Yan Lin
Lianqiang Che
Zhengfeng Fang
Bin Feng
Jian Li
Jianping Wang
De Wu
Zhihua Ren
author_facet Shengyu Xu
Xiaoling Wu
Yanpeng Dong
Mengmeng Xu
Zimei Li
Sirun Chen
Yong Zhuo
Yan Lin
Lianqiang Che
Zhengfeng Fang
Bin Feng
Jian Li
Jianping Wang
De Wu
Zhihua Ren
author_sort Shengyu Xu
collection DOAJ
description Abstract Background We have previously found that the energy level in sows affects the activation of primordial follicles. Glucose is the primary metabolic substrate of dietary energy and its effect and mechanism of action with regards to the activation and development of primordial follicle remain unclear. Studies utilizing several different animal cells have shown that energy stress, induced by glucose starvation, activates AMPK and participates in a variety of cellular processes by regulating the Hippo and mTOR signaling pathways. However, whether glucose can affect primordial follicle activation through the above pathways has not been reported. Methods We developed an in vitro culture system for mouse ovaries to investigate the effects of glucose on the primordial follicle activation. Protein expression of AMPK‐Hippo‐YAP and AMPK‐mTOR pathway was investigated under glucose starvation and optimal glucose level treatment. Then, ovaries were treated with AICAR or Compound C in vitro to explore the effect of AMPK activation or inhibition on primordial follicle activation, and the changes of AMPK‐Hippo‐YAP and AMPK‐mTOR signaling pathways. Finally, investigated the signaling pathways affected by glucose potentially affecting the primordial follicle activation in vivo. Results The glucose was an essential nutrient for primordial follicle activation and we identified 25 mM glucose as the optimal level (P < .05) for the primordial follicle activation in vitro. The glycolysis pathway was involved in primordial follicle activation (P < .05) of ovaries cultured in vitro. The glucose affected the activation of primordial follicles in vitro through AMPK/mTOR signaling pathway by AMPK activation or inhibition treatment and follicle ratio count (P < .05). Moreover, glucose affected the primordial follicle activation of ovary in vivo via mTOR signaling pathway. Conclusions This study demonstrates that glucose affects the primordial follicle activation through the AMPK/mTOR rather than the AMPK/Hippo signaling pathway.
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spelling doaj.art-5d648e6bf2354689bcd74555e571cb0b2022-12-21T23:35:18ZengWileyClinical and Translational Medicine2001-13262020-07-01103n/an/a10.1002/ctm2.122Glucose activates the primordial follicle through the AMPK/mTOR signaling pathwayShengyu Xu0Xiaoling Wu1Yanpeng Dong2Mengmeng Xu3Zimei Li4Sirun Chen5Yong Zhuo6Yan Lin7Lianqiang Che8Zhengfeng Fang9Bin Feng10Jian Li11Jianping Wang12De Wu13Zhihua Ren14Animal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaAnimal Nutrition Institute, Sichuan Agricultural University; Key Laboratory of Animal Disease‐resistant Nutrition, Ministry of Education Ministry of Agriculture and Rural Affairs, Sichuan Province Chengdu Sichuan P. R. ChinaCollege of Veterinary Medicine, Sichuan Province Key Laboratory of Animal Disease and Human Health, Key Laboratory of Environmental Hazard and Human Health of Sichuan Province Sichuan Agricultural University Chengdu Sichuan P. R. ChinaAbstract Background We have previously found that the energy level in sows affects the activation of primordial follicles. Glucose is the primary metabolic substrate of dietary energy and its effect and mechanism of action with regards to the activation and development of primordial follicle remain unclear. Studies utilizing several different animal cells have shown that energy stress, induced by glucose starvation, activates AMPK and participates in a variety of cellular processes by regulating the Hippo and mTOR signaling pathways. However, whether glucose can affect primordial follicle activation through the above pathways has not been reported. Methods We developed an in vitro culture system for mouse ovaries to investigate the effects of glucose on the primordial follicle activation. Protein expression of AMPK‐Hippo‐YAP and AMPK‐mTOR pathway was investigated under glucose starvation and optimal glucose level treatment. Then, ovaries were treated with AICAR or Compound C in vitro to explore the effect of AMPK activation or inhibition on primordial follicle activation, and the changes of AMPK‐Hippo‐YAP and AMPK‐mTOR signaling pathways. Finally, investigated the signaling pathways affected by glucose potentially affecting the primordial follicle activation in vivo. Results The glucose was an essential nutrient for primordial follicle activation and we identified 25 mM glucose as the optimal level (P < .05) for the primordial follicle activation in vitro. The glycolysis pathway was involved in primordial follicle activation (P < .05) of ovaries cultured in vitro. The glucose affected the activation of primordial follicles in vitro through AMPK/mTOR signaling pathway by AMPK activation or inhibition treatment and follicle ratio count (P < .05). Moreover, glucose affected the primordial follicle activation of ovary in vivo via mTOR signaling pathway. Conclusions This study demonstrates that glucose affects the primordial follicle activation through the AMPK/mTOR rather than the AMPK/Hippo signaling pathway.https://doi.org/10.1002/ctm2.122AMPKglucoseHippo signaling pathwaymTOR signaling pathwayovary culture in vitroprimordial follicle activation
spellingShingle Shengyu Xu
Xiaoling Wu
Yanpeng Dong
Mengmeng Xu
Zimei Li
Sirun Chen
Yong Zhuo
Yan Lin
Lianqiang Che
Zhengfeng Fang
Bin Feng
Jian Li
Jianping Wang
De Wu
Zhihua Ren
Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway
Clinical and Translational Medicine
AMPK
glucose
Hippo signaling pathway
mTOR signaling pathway
ovary culture in vitro
primordial follicle activation
title Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway
title_full Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway
title_fullStr Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway
title_full_unstemmed Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway
title_short Glucose activates the primordial follicle through the AMPK/mTOR signaling pathway
title_sort glucose activates the primordial follicle through the ampk mtor signaling pathway
topic AMPK
glucose
Hippo signaling pathway
mTOR signaling pathway
ovary culture in vitro
primordial follicle activation
url https://doi.org/10.1002/ctm2.122
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