Granulosa cell MYC maintains oocyte developmental ability via promoting glycerophospholipid metabolism in mice

Granulosa cell-produced metabolites maintain the growth and development of mammalian oocytes. In the present study, the cellular-myelocytomatosis viral oncogene (c- Myc, also known as Myc ) mRNA was mainly expressed in granulosa cells of mouse follicles. To investigate the role of MYC in MGCs, we generated the mice with conditional Myc deletion in granulosa cells. The knockout mice showed a decrease in the number of ovulations, and the fertilized oocytes failed to develop normally into blastocysts, resulting in female infertility. Further studies revealed that the knockout of Myc decreased the mRNA and protein levels of genes related to glycerophospholipid metabolic enzymes in MGCs. Consistent with this, the knockout of Myc reduced the glycerophospholipid metabolites in MGCs, resulting in the decrease of glycerophospholipid metabolites and mitochondrial functions, and then the increase of abnormal spindle assembly and aneuploidy in oocytes. The addition of glycerophospholipid metabolites in cultured cumulus–oocyte complex could partially reverse the blastocyst rate of knockout mouse oocytes undergoing in vitro fertilization. These findings demonstrate that MYC-promoted glycerophospholipid in MGCs maintain oocyte developmental ability.