Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos.
Optimal development of fertilized eggs into preimplantation embryos is essential for reproduction. Although mammalian oocytes ovulated after luteinizing hormone (LH) stimulation can be fertilized and promoted into early embryos in vitro, little is known about ovarian factors important for the conditioning of eggs for early embryo development. Because LH interacts only with ovarian somatic cells, its potential regulation of oocyte functions is presumably mediated by local paracrine factors. We performed DNA microarray analyses of ovarian transcripts and identified brain-derived neurotrophic factor (BDNF) secreted by granulosa and cumulus cells as an ovarian factor stimulated by the preovulatory LH surge. Ovarian BDNF acts on TrkB receptors expressed exclusively in oocytes to enhance first polar body extrusion of oocytes and to promote the in vitro development of zygotes into preimplantation embryos. Furthermore, in vivo treatment with a Trk receptor inhibitor suppressed first polar body extrusion and the progression of zygotes into blastocysts. Thus, ovarian BDNF is important to nuclear and cytoplasmic maturation of the oocyte, which is essential for successful oocyte development into preimplantation embryos. Treatment with BDNF could condition the cultured oocytes for optimal progression into the totipotent blastocysts.
Kawamura
Kazuhiro
K
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Kawamura
Nanami
N
Mulders
Sabine M
SM
Sollewijn Gelpke
Maarten D
MD
Hsueh
Aaron J W
AJ
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005306:Fertilization; D006062:Gonadotropins / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000378:metabolism*; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D010060:Ovulation; D020800:Receptor, Nerve Growth Factor; D020813:Receptor, trkB / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D006062:Gonadotropins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D007986:Luteinizing Hormone; D020813:Receptor, trkB