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, 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, TNFAIP6, 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. (Fertil Steril (R) 2010;93:1394-406. (C)2010 by American Society for Reproductive Medicine.)