title: Differences in transcriptomic profiles of human cumulus cells isolated from oocytes at GV, MI and MII stages after in vivo and in vitro oocyte maturation.
abstract: BACKGROUND
  Oocyte maturation and competence to development depends on its close relationship with cumulus cells (CCs). However, the maturation conditions of human cumulus-oocyte complexes (COCs) might affect gene expression in both oocyte and CCs. We thus compared the transcriptome profiles of CCs isolated from in vivo and in vitro matured COCs at different nuclear maturation stages.
  
  
  METHODS
  Three groups of CCs from patients who underwent ICSI were included: CCs of patients with polycystic ovary syndrome (PCOS) referred for in vitro maturation (IVM), CCs from patients with PCOS for in vivo maturation (used as controls) and CCs from normal responders referred for in vivo maturation. CCs were isolated from COCs at the germinal vesicle, metaphase I and metaphase II stages. Microarray technology was used to analyse the global gene expression and significance analysis of microarray to compare the expression profiles of CCs from COCs at different nuclear maturation stages following IVM or in vivo maturation. Selected genes were validated by RT-qPCR.
  
  
  RESULTS
  In CCs isolated after IVM, genes related to cumulus expansion and oocyte maturation, such as EREG, AREG and PTX3, were down-regulated, while cell cycle-related genes were up-regulated in comparison with CCs from in vivo matured COCs from PCOS and normal responder patients. Moreover, irrespective of the stage of oocyte maturation, genes involved in DNA replication, recombination and repair were up-regulated in CCs after IVM.
  
  
  CONCLUSIONS
  The CC transcriptomic signature varies according to both the oocyte maturation stage and the maturation conditions. Our findings suggest a delay in the acquisition of the mature CC phenotype following IVM, opening a new perspective for the improvement in IVM conditions.
authors.affiliation: CHU Montpellier, Institute for Research in Biotherapy, Hôpital Saint-Eloi, and Université Montpellier 1, UFR de Médecine, Montpellier F-34295, France.
authors.forename: Zamalou Gisèle
authors.initials: ZG
authors.lastname: Ouandaogo
authors.forename: Nelly
authors.initials: N
authors.lastname: Frydman
authors.forename: Laetitia
authors.initials: L
authors.lastname: Hesters
authors.forename: Said
authors.initials: S
authors.lastname: Assou
authors.forename: Delphine
authors.initials: D
authors.lastname: Haouzi
authors.forename: Hervé
authors.initials: H
authors.lastname: Dechaud
authors.forename: René
authors.initials: R
authors.lastname: Frydman
authors.forename: Samir
authors.initials: S
authors.lastname: Hamamah
mesh_terms: D000328:Adult; D054885:Cumulus Cells / Q000166:cytology*; D046149:Embryo Culture Techniques / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D009866:Oogenesis / Q000502:physiology; D006080:Ovarian Follicle / Q000166:cytology*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000628:therapy; D016133:Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014158:Transcription, Genetic