title: Differential granulosa cell gene expression in young women with diminished ovarian reserve.
abstract: OBJECTIVE
  To investigate if a diagnosis of diminished ovarian reserve (DOR) is associated with a differential gene profile of ovarian granulosa cells (GCs) in infertile women undergoing in vitro fertilization (IVF).
  
  
  METHODS
  Prospective Cohort Study.
  
  
  METHODS
  Academic IVF Program.
  
  
  METHODS
  Infertile women <38 years were prospectively enrolled into 2 groups: normal ovarian reserve (NOR, follicle-stimulating hormone [FSH] < 10 mIU/mL, n = 4) and DOR (FSH ≥ 10.0 mIU/mL, n = 4).
  
  
  METHODS
  Cumulus (C) and mural (M) GCs were isolated at egg retrieval; messenger RNA was extracted and transcribed.
  
  
  METHODS
  Differential gene expression in cerebellar granule cells (CGCs) in the 2 groups was assessed by cDNA microarray. Microarray findings were validated by quantitative real-time polymerase chain reaction (qRTPCR) in CGCs and explored in multinucleated giant cells (MGCs).
  
  
  RESULTS
  Of the 1256 differentially regulated genes identified in CGCs of women with DOR, the insulin-like growth factor (IGF) family was a biologically relevant gene family of a priori interest. Downregulation of IGF1 and IGF2 ligands (-3.28- and -2.54-fold, respectively), and their receptors, (-3.53- and -1.32-fold downregulation of IGF1R and IGF2R, respectively) was identified in luteinized CGCs in women with DOR compared to those with NOR. Downregulation of both IGF1 and IGF 2 ligands (-4.35- and 3.89-fold, respectively) was furthermore observed in MGCs in women with DOR compared to those with NOR; no differences in the expression of respective receptors were however observed in MGCs in the 2 groups.
  
  
  CONCLUSIONS
  Components of the IGF gene family are downregulated in GCs of women with DOR. These findings maybe contributory to the reproductive compromise observed in women with DOR, and merit further exploration.
authors.affiliation: Reproductive Endocrinology & Infertility, Department ofObstetrics, Gynecology & Women’s Health, Albert Einstein Collegeof Medicine, Bronx, NY, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Greenseid
authors.forename: Sangita
authors.initials: S
authors.lastname: Jindal
authors.forename: Joshua
authors.initials: J
authors.lastname: Hurwitz
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
authors.forename: Lubna
authors.initials: L
authors.lastname: Pal
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017451:Receptors, Somatomedin / Q000096:biosynthesis* / Q000235:genetics; D013002:Somatomedins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D013002:Somatomedins