Differential granulosa cell gene expression in young women with diminished ovarian reserve

Keri Greenseid, Sangita Jindal, Joshua Hurwitz, Nanette Santoro, Lubna Pal

Research output: Contribution to journalArticle

20 Scopus citations

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). Design: Prospective Cohort Study. Setting: Academic IVF Program. Patients: 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). Interventions: Cumulus (C) and mural (M) GCs were isolated at egg retrieval; messenger RNA was extracted and transcribed. Main Outcome Measure(s): 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.

Original languageEnglish (US)
Pages (from-to)892-899
Number of pages8
JournalReproductive Sciences
Volume18
Issue number9
DOIs
StatePublished - Sep 1 2011

Keywords

  • cumulus
  • diminished ovarian reserve
  • gene expression
  • granulosa cell
  • insulin-like growth factor
  • microarray
  • mural
  • ovary

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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