title: Impact of maternal aging on the molecular signature of human cumulus cells.
abstract: OBJECTIVE
  To investigate the impact of maternal aging on the molecular signature of cumulus cells.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Patients, young fertile oocyte donors (n = 40) and infertile women of advanced maternal age (40-45 years; n = 48), donated, with Institutional Review Board consent, cumulus cells during routine infertility treatment.
  
  
  METHODS
  None.
  
  
  METHODS
  Proteomic and gene expression profiles of cumulus cells.
  
  
  RESULTS
  Proteomic analysis identified a total of 1,423 cumulus cell proteins. Statistical analysis revealed 110 (7.7%) proteins to be differentially expressed in relation to female aging (>1.5-fold change). Pathway annotation revealed significant involvement in metabolism (ACAT2, HSD17B4, ALDH9A1, MVK, CYP11A1, and FDFT1), oxidative phosphorylation (OP; NDUFA1, UQCRC1, MT-ATP6, ATP5I, and MT-ATP8), and post-transcriptional mechanisms (KHSRP, SFPQ, DDX46, SNRPF, ADAR, NHPL1, and U2AF2) relative to advanced maternal age. Gene expression analysis also revealed altered profiles in cumulus cells from women in their early to mid-40s.
  
  
  CONCLUSIONS
  This novel study reveals that the cumulus cell molecular signature, at both the gene and protein level, is impacted by advanced maternal aging. A compromised follicular environment is evident with altered energy metabolism and post-transcriptional processes.
authors.affiliation: National Foundation for Fertility Research, Lone Tree, Colorado, USA.
authors.forename: Susanna
authors.initials: S
authors.lastname: McReynolds
authors.forename: Monika
authors.initials: M
authors.lastname: Dzieciatkowska
authors.forename: Blair R
authors.initials: BR
authors.lastname: McCallie
authors.forename: Shane D
authors.initials: SD
authors.lastname: Mitchell
authors.forename: John
authors.initials: J
authors.lastname: Stevens
authors.forename: Kirk
authors.initials: K
authors.lastname: Hansen
authors.forename: William B
authors.initials: WB
authors.lastname: Schoolcraft
authors.forename: Mandy G
authors.initials: MG
authors.lastname: Katz-Jaffe
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism*; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D008423:Maternal Age; D008875:Middle Aged; D018587:Oocyte Donation; D020543:Proteome / Q000378:metabolism*
chemical_list: D020543:Proteome