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Brain-derived neurotrophic factor is a regulator of human oocyte maturation and early embryo development.

TitleBrain-derived neurotrophic factor is a regulator of human oocyte maturation and early embryo development.
Publication TypeJournal Article
Year of Publication2010
AuthorsAnderson RA, Bayne R, Gardner J, de Sousa P
JournalFertil Steril
Volume93
Issue5
Pagination1394-406
Date Published2010 Mar 15
ISSN1556-5653
KeywordsAdult, Blastocyst, Brain-Derived Neurotrophic Factor, Cells, Cultured, Cleavage Stage, Ovum, Cumulus Cells, Embryo Culture Techniques, Female, Gene Expression Regulation, Developmental, Humans, Morula, Oocytes, Parthenogenesis, Prospective Studies, Receptor, trkB, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Signal Transduction, Time Factors, Young Adult
Abstract

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.

DOI10.1016/j.fertnstert.2009.04.007
Alternate JournalFertil. Steril.
PubMed ID19463996
Grant ListG0300484 / / Medical Research Council / United Kingdom
MC_U127684439 / / Medical Research Council / United Kingdom
U.1276.00.002.00001.01(61015) / / Medical Research Council / United Kingdom
WBS U.1276.00.002.00001.01 / / Medical Research Council / United Kingdom