title: Reduced neurotrophin receptor tropomyosin-related kinase A expression in human granulosa cells: a novel marker of diminishing ovarian reserve.
abstract: OBJECTIVE
  To determine whether human mural and cumulus granulosa cell neurotrophin and neurotrophin receptor content correlate to ovarian reserve markers.
  
  
  METHODS
  Prospective, laboratory-based study.
  
  
  METHODS
  Academic assisted reproductive technology (ART) program.
  
  
  METHODS
  Twenty-three women undergoing ART.
  
  
  METHODS
  Mural and cumulus granulosa cells were collected from women undergoing oocyte retrieval during ART cycles. Relative messenger RNA (mRNA) levels of neurotrophins and their receptors were measured by quantitative reverse transcription-polymerase chain reaction and correlated to serum antimüllerian hormone (AMH) levels and the number of oocytes retrieved.
  
  
  METHODS
  Number of oocytes retrieved.
  
  
  RESULTS
  Mural and cumulus granulosa cell nerve growth factor receptor tropomyosin-related kinase A (TrkA) mRNA correlated strongly to the number of oocytes retrieved. Similarly, higher serum AMH was associated with higher cumulus granulosa cell TrkA mRNA. Both mural and cumulus granulosa cell p75(NTR)/TrkA ratios were lower in women with higher serum AMH, and the number of oocytes retrieved was greater among women with low p75(NTR)/TrkA ratio. No significant associations were found between brain-derived neurotrophic factor (BDNF) and its specific receptor tropomyosin-related kinase B (TrkB) and ovarian reserve markers. Although BDNF and TrkB expression were higher in cumulus compared with mural granulosa cells, no such association was found between TrkA and granulosa cells. Antimüllerian hormone and cumulus TrkA mRNA, in a model incorporating both, correlated strongly to the number of oocytes retrieved (R(2) = 0.84).
  
  
  CONCLUSIONS
  Cumulus TrkA and p75(NTR) mRNA correlate to ovarian reserve, whereas BDNF and TrkB are associated with the type of granulosa cell.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Montefiore Institute for Reproductive Medicine and Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA. erbuyuk@yahoo.com
authors.forename: Erkan
authors.initials: E
authors.lastname: Buyuk
authors.forename: Nanette
authors.initials: N
authors.lastname: Santoro
authors.forename: Hillel W
authors.initials: HW
authors.lastname: Cohen
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.forename: Sangita
authors.initials: S
authors.lastname: Jindal
mesh_terms: D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005819:Genetic Markers; D006107:Granulosa Cells / Q000201:enzymology*; D006801:Humans; D020932:Nerve Growth Factor / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D054315:Oocyte Retrieval; D010053:Ovary / Q000201:enzymology* / Q000503:physiopathology; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics*; D020813:Receptor, trkB / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D005819:Genetic Markers; C502240:NGF protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D054304:Anti-Mullerian Hormone; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB