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.

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, E₂), 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.

Key Words: Oocyte, in vitro maturation, parthenogenesis, brain-derived neurotrophic factor