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Published on: October 1, 2007
Brain-derived neurotrophic factor is a regulator of human oocyte maturation and early embryo development
Richard A Anderson1, Rosemary A L Bayne, John Gardner
1Division of Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
Objective:
To investigate a role for brain-derived neurotrophic factor (BDNF) in human oocyte maturation.
Design:
Prospective study.
Setting:
Research institute.
Patients:
Women undergoing laparoscopic sterilization.
Intervention(S):
Small antral follicle cumulus-oocyte complexes (COCs) were matured in vitro (IVM) to metaphase II (MII) in media with hormones (H; FSH, LH, E(2)), serum replacement (SR), BDNF, or blocking antibodies to BDNF (BDNF/AB and TrkB/Fc), and activated.
Main Outcome Measure(S):
The COCs were analyzed for expression of neurotrophin ligands/receptors and cumulus genes (HAS2, TNFAlP6, PTGS2, GREM1) by reverse transcription-polymerase chain reaction (RT-PCR), cumulus expansion, maturation to MII, and parthenogenetic embryo development.
Result(S):
The BDNF and truncated TrkB receptor were expressed in cumulus and mature oocytes. There was no difference in MII yields after IVM in control (H + SR) versus H + BDNF, H + SR + BDNF, or BDNF + SR media. However, both BDNF/AB and TrkB/Fc improved MII yields. After activation, normal cleavage was highest in H + SR (38%), whereas blocking antibodies yielded the highest abnormal cleavage (BDNF/AB 68%; TrkB/Fc 57%). Failure to cleave was highest in H + BDNF + SR (92%). Only H + SR yielded morulae/blastocysts (6%). Expression of GREM1 in cumulus increased after IVM in H + BDNF versus H + SR or in vivo maturation.
Conclusion(S):
The BDNF signaling within COCs influences oocyte maturation and early embryogenesis.
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