Brain-derived neurotrophic factor is a regulator of human oocyte maturation and early embryo development.
OBJECTIVE
To investigate a role for brain-derived neurotrophic factor (BDNF) in human oocyte maturation.


METHODS
Prospective study.


METHODS
Research institute.


METHODS
Women undergoing laparoscopic sterilization.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The BDNF signaling within COCs influences oocyte maturation and early embryogenesis.
Anderson
Richard A
RA
Division of Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
Bayne
Rosemary A L
RA
Gardner
John
J
De Sousa
Paul A
PA
D000328:Adult; D001755:Blastocyst / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002970:Cleavage Stage, Ovum / Q000378:metabolism*; D054885:Cumulus Cells / Q000378:metabolism*; D046149:Embryo Culture Techniques; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D009028:Morula / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism*; D010312:Parthenogenesis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D020813:Receptor, trkB