title: The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women.
abstract: BACKGROUND
  Corona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls.
  
  
  METHODS
  All patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays.
  
  
  RESULTS
  The transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5).
  
  
  CONCLUSIONS
  The overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications.
authors.affiliation: Department of Gynecology-Obstetrics, Holbaek Fertility Clinic, Holbaek Hospital, Smedelundsgade 60, 4300, Holbaek, Denmark. mlwi@regionsjaelland.dk.
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Wissing
authors.affiliation: Institute of Biology, University of Copenhagen, 2100, Copenhagen, Denmark. ssonne@bio.ku.dk.
authors.forename: Si Brask
authors.initials: SB
authors.lastname: Sonne
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet building 208, 2800, Lyngby, Denmark. David@harsk.dk.
authors.forename: David
authors.initials: D
authors.lastname: Westergaard
authors.affiliation: DTU Multi Assay Core, Technical University of Denmark DTU, 2800, Lyngby, Denmark. khodo@cbs.dtu.dk.
authors.forename: Kho do
authors.initials: Kd
authors.lastname: Nguyen
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Kemitorvet building 208, 2800, Lyngby, Denmark. belling@cbs.dtu.dk.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Belling
authors.affiliation: Department of Gynecology-Obstetrics, Holbaek Fertility Clinic, Holbaek Hospital, Smedelundsgade 60, 4300, Holbaek, Denmark. tht@regionsjaelland.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Høst
authors.affiliation: Department of Gynecology-Obstetrics, Holbaek Fertility Clinic, Holbaek Hospital, Smedelundsgade 60, 4300, Holbaek, Denmark. aleg@regionsjaelland.dk.
authors.forename: Anne Lis
authors.initials: AL
authors.lastname: Mikkelsen
mesh_terms: D000328:Adult; D001755:Blastocyst / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000378:metabolism / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020554:Sperm Injections, Intracytoplasmic; D059467:Transcriptome; D055815:Young Adult