Differential regulation of cumulus cell transcription during oocyte maturation in vivo and in vitro

Differences in cumulus cell gene expression after oocyte maturation in vitro (IVM) or in vivo have been described in previous studies. However, the possible impact of follicle stage on gene expression deregulation during human oocyte IVM remains unknown. Expression of selected genes of interest was compared in cumulus cell of three classes of human cumulus cell-oocyte complexes (COCs): a) COCs derived from human chorionic gonadotropin (hCG)-triggered IVM cycles, collected at the germinal vesicle (GV) stage from mid-sized follicles (4-12 mm) and matured in vitro (IVM-GV); b) COCs derived from hCG-triggered IVM cycles, collected from mid-sized follicles (4-12 mm) and matured in vivo (IVM-MII); c) COCs derived from controlled ovarian stimulation in vitro fertilization (IVF) cycles, collected from large/preovulatory follicles and matured in vivo (IVF-MII). Overall, mRNA levels of the large majority of the 20 genes of different regulative and metabolic pathways subject to analysis were altered in IVM samples compared with in vivo matured COCs. In some cases, follicle size appeared to have a role in determining transcription deregulation. For example, in comparison to the IVF-MII control, the luteinizing hormone receptor was largely overexpressed in both IVM-GV and IVM-MII COCs, therefore irrespective of IVM. However, in other circumstances follicle size and IVM had distinct and opposite impacts on gene expression, as shown by transcription of amphiregulin, which was increased in IVM-MII COCs, but decreased in COCs matured in vitro (IVM-GV) compared with the IVF-MII control. This study confirms and extends previous data on gene expression dysregulation during IVM and indicates that the size of follicles from which immature oocytes are retrieved can be an independent factor of differential transcriptional regulation.