The Discovery And Biological Significance Of Energy Storage Behavior In Granulosa Cells

Follicular granulosa cells(f GCs)have luteinizing hormone(LH)receptors,which are key cells in the follicle that respond to ovulation signals and drive the ovulation process.Most luteal cells are differentiated by f GCs in response to LH signals,and their progesterone secretion by f GCs plays an important role in embryo implantation and development as well as pregnancy maintenance.In this study,we analyzed the transcriptomic data of ovulation in different species and found that the energy metabolism of granulosa cells during ovulation has a certain change pattern.And its application in livestock production,the specific results of the study are as follows:(1)Firstly,the transcriptome data of mouse,bovine and human showed that energy metabolism and energy production were inhibited in early ovulatory f GCs,moreover,this pattern of energy changes in f GCs was conservative among species;(2)Subsequent experimental validation of the transcriptome data showed that the metabolic activities of various endomembrane organelles(er,Golgi apparatus,lysosomes and mitochondria)in f GCs were inhibited in response to ovulation signals;the tricarboxylic acid cycle and glycolysis processes were also inhibited,and the energy-consuming metabolism and energy synthesis of granulosa cells were reduced;(3)Further experiments revealed an increase in glycogen and lipid droplet content in granulosa cells in response to ovulation signals,and this newly discovered cytological phenomenon was named "granulosa cell energy storage" in this study;(4)Enhanced granulosa cell energy storage during ovulation by glucose injection revealed enhanced granulosa cell corpus luteum function;(5)Next,we found that the Insulin/IGF1 signaling pathway is involved in the regulation of energy changes during ovulation,and that enhancement or inhibition of this pathway with insulin and BMS-536924 altered the energy reserve of granulosa cells;(6)Finally,this study investigated the application of the phenomenon of "granulosa cell energy storage" in livestock production,and found that glucose injection at the same time as ovulation improved the quality of embryo development and thus the efficiency of embryo transfer in mice.Similarly,the results of glucose supplementation to improve luteal function in sheep were also initially validated.In summary,this study identified a novel biological phenomenon during ovulation,namely,a decrease in energy-consuming metabolism and energy production and an increase in glycogen and lipid droplet reserves in granulosa cells in response to ovulation signals,which was named"granulosa cell energy storage".Further,this study revealed that the purpose of granulosa cell energy storage is for luteal use and experimentally confirmed the involvement of Insulin/IGF1 signaling pathway in regulating"granulosa cell energy storage".In this study,a preliminary application of glucose to enhance granulosa cell energy storage in mice was investigated,which provides a new idea to improve the function of corpus luteum.