Single Human Oocyte And Cumulus Cells Transcriptomics Reveal The Stage-dependent Energy Metabolism Dynamics During Oocyte Maturation Before Ovulation

For human reproduction,a fully developed oocyte is indispensable.The maturation of the oocyte located in the center of the cumulus-oocyte complex(COC)is an extraordinarily complicated process that depends on not only the oocyte itself but also crosstalk between the oocyte and the surrounding cumulus granulose cells(CCs).However,the energetic crosstalk between the oocyte and CCs during oocyte maturation remains unclear.Here,we performed micro-transcriptomic profiling of oocyte and their CCs from 47 preimplantation genetic testing for aneuploidy(PGT-A)patients to explore the relationship between energy metabolism in the oocyte and CCs at different maturation stages(GV,MI and MII).We found that oocyte maturation was a dynamic process and MI oocyte may be subdivided into early MI oocyte and late MI oocyte.The energy consumption of GV oocyte was relatively vigorous.Due to glycolysis in CCs was more active than oocyte during this period,it was speculated that CCs may provide the main energy source through glycolysis.Interestingly,we found that the expression of genes related to fatty acids(FAs)and cholesterol metabolism pathways were significantly increased in CCs at the late stage of oocyte maturation,which suggested that FAs and cholesterol-based lipid metabolism biological processes were active.FAs are stored in follicles in the form of lipid droplets(LDs)and may be a more efficient source of energy for oocyte and even embryogenesis.Moreover,cholesterol provided local high progesterone for mature oocyte in preparation for fertilization.Taken together,our data suggested that oocyte underwent dramatic changes in the transcriptome during maturation from GV-MII,with less changes occurred in CCs during this process.CCs may not only provide energy substrates through glycolysis during the GV phase,but also synthesize lipids and progesterone in late oocyte maturation to aid fertilization and embryonic development.It provides a reference for further study on the metabolic interaction between oocyte and CCs in maturation and development by revealing unique features in the transcriptional machinery of oocyte and CCs during oocyte maturation.