Granulosa cell glycogen fuels the avascular corpus luteum
Abstract
The corpus luteum (CL) arises from the luteinization of granulosa cells (GCs) and theca cells, marked by rapid progesterone elevation and angiogenesis. Intriguingly, angiogenesis lags behind progesterone elevation, creating an avascular phase during which luteal cells must fuel intensive steroidogenesis without perfusion. How the avascular CL meets this energetic demand remains a mystery. Here, we reveal a cellular adaptive mechanism—granulosa cell energy storage (GCES)—that resolves this enigma. We demonstrate that upon luteinization initiation, GCs enter a metabolically quiescent state yet enhance glucose uptake, converting the glucose into glycogen. Catabolism of this glycogen reserve supplies the energy required for the avascular CL, ensuring normal luteogenesis. Disruption of GCES induces luteal insufficiency, whereas timely glucose administration enhances GCES, improving luteal function and optimizing reproductive outcome in both mouse and ovine models. In human study, oral intake of glucose post-hCG significantly augments GCES and enhances progesterone production. These results advance our understanding of luteinization.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (22)
Jianning Liao
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Qinghua Liu
National Synchrotron Radiation Laboratory
Cong Liu
Guiqiong Liu
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Xiang Li
Xiaodong Wang
CAS Key Laboratory of Science and Technology on Applied Catalysis
Yaqin Wang
Centre for Reproductive Medicine, Renmin Hospital of Wuhan University
Ruiyan Liu
College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China
Hao Wu
Chaoli Wang
Xinjiang Western Animal Husbandry Co., Ltd
Hongru Shi
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Yongheng Zhao
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Wenkai Ke
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Zaohong Ran
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Zian Wu
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Bowen Tan
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering
Quanfeng Wang
Xinjiang Jinken Aoqun Agriculture and Animal Husbandry Technology Co., Ltd
Guohua Hua
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University
Shujun Zhang
Qingzhen Xie
Centre for Reproductive Medicine, Renmin Hospital of Wuhan University
Guoshi Liu
Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University
Changjiu He
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University