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

Mol Reprod Dev. 2025 Jun;92(6):e70035. doi: 10.1002/mrd.70035.

Abstract

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.

Keywords: Human IVM; cumulus cells; microarray; oocyte maturation; unstimulated ovaries.

MeSH terms

  • Adult
  • Cumulus Cells* / cytology
  • Cumulus Cells* / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • In Vitro Oocyte Maturation Techniques*
  • Oocytes* / cytology
  • Oocytes* / metabolism
  • Signal Transduction / physiology
  • Transcription, Genetic* / physiology
  • Young Adult