Differential expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB in luteinized human mural and cumulus granulosa cells

Abstract

OBJECTIVE: Characterization of human luteinized mural and cumulus granulosa cell expression of neurotrophins nerve growth factor (NGF) and (BDNF) and their receptors TrkA, TrkB and p75NTR. DESIGN: Prospective clinical and laboratory study. MATERIALS AND METHODS: Mural and cumulus granulosa cells were collected from 23 women (age range: 26-46) undergoing controlled ovarian hyperstimulation (COH) in preparation for ART. Fifteen women with male or tubal factor infertility and 8 women with diminished ovarian reserve (DOR, diagnosed by day 3 FSH>10IU/L) were included. Mural and cumulus cell mRNA was isolated and gene expression of NGF, BDNF, TrkA, TrkB and p75NTR was quantified and normalized to GAPDH by qRT-PCR. Data were analyzed using correlation analysis as appropriate, Student t–test and expressed as Mean ± SEM. RESULTS: BDNF mRNA expression was almost 2-fold higher in cumulus than in mural cells (6.4 ± 0.9 vs 3.5 ± 0.5, p=0.004). Similarly, expression of the BDNF receptor TrkB was almost 3–fold higher in cumulus than in mural cells (71.6 ± 8.9 vs 25.4 ± 4.5, p<0.0001). Conversely, expression of NGF, its receptor TrkA, and the common low affinity receptor p75NTR was not different in mural and cumulus granulosa cells. BDNF and TrkB expression levels were not associated with the maximum historical FSH, AMH or number of oocytes retrieved during COH-ART cycles. CONCLUSION: We demonstrate for the first time that expression of BDNF and its receptor TrkB is significantly increased in cumulus vs mural granulosa cells. We also demonstrate a lack of association between BDNF/TrkB mRNA levels and clinical indicators of DOR. Further experiments are needed to determine whether BDNF and TrkB are important in cumulus granulosa cell differentiation.