Transcriptional Changes in Cumulus Cells During In Vitro Maturation of Human Oocytes

This study assessed transcriptional changes in human cumulus cells (CCs) during oocyte maturation In Vitro. CCs were collected from 25 cumulus-oocyte complexes derived from surplus ovarian medulla tissue of eight women (mean age 29 years, range 19-36) undergoing ovarian tissue cryopreservation without ovarian stimulation. Samples included CCs from fresh germinal vesicle (GV) oocytes (n = 5), and from GV (n = 8) and metaphase II (MII) oocytes (n = 12) after 48 h of In Vitro maturation (IVM). Microarray analysis revealed active signaling pathways during IVM, emphasizing LHCGR upregulation as central to oocyte maturation. Enhanced pathways included the insulin-like growth factor (IGF) system, particularly IGF2, and activin/inhibin signaling, while others appeared less active In Vitro compared to In Vivo. Differential expression analysis identified 1763 significantly expressed genes (DEGs) between fresh GV and MII-IVM, 50 DEGs between GV-IVM and MII-IVM, and 339 novel or unknown transcripts. Clustering highlighted additional pathways, such as MAPK, PPAR, Wnt, cholesterol metabolism, PI3K-AKT, TGF-β, focal adhesion, actin cytoskeleton regulation, and RANK/RANKL, with differential regulation during IVM. These findings underscore the complexity of signaling in CCs and the distinct regulatory mechanisms of human oocyte maturation In Vitro compared to In Vivo.