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.

Design: Prospective, laboratory-based study.

Setting: Academic assisted reproductive technology (ART) program.

Patient(s): Twenty-three women undergoing ART.

Intervention(s): 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.

Main outcome measure(s): Number of oocytes retrieved.

Result(s): 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).

Conclusion(s): Cumulus TrkA and p75(NTR) mRNA correlate to ovarian reserve, whereas BDNF and TrkB are associated with the type of granulosa cell.