Regulation of preimplantation embryo development by brain-derived neurotrophic factor. 2007

Kazuhiro Kawamura, and Nanami Kawamura, and Jun Fukuda, and Jin Kumagai, and Aaron J W Hsueh, and Toshinobu Tanaka
Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita, 010-8543, Japan. kawamura@yf7.so-net.ne.jp

Hormonal factors secreted by embryos and reproductive tracts are important for successful development of preimplantation embryos. We found expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) transcripts at its highest levels in the blastocyst stages. The transcripts for their receptor, TrkB, were detectable throughout the early embryonic stages with an increase after the early blastocyst stage. Both BDNF and TrkB are expressed in trophectoderm cells, whereas ligand-binding studies indicated specific binding of BDNF to trophectoderm cells. Furthermore, BDNF and NT-4/5 were produced in pregnant oviducts and uteri. Treatment with BDNF promoted the development of two-cell-stage embryos into blastocysts showing increased proliferation and decreased apoptosis. The effects of BDNF were blocked by the TrkB ectodomain or a Trk receptor inhibitor, K252a. Studies using specific inhibitors demonstrated the roles of the PI3K, but not the ERK, pathway in mediating BDNF actions. Under high-density embryo cultures, treatment with the TrkB ectodomain or K252a alone also inhibited embryonic development and survival, suggesting potential autocrine actions of BDNF produced by the embryo. In vivo experiments further demonstrated that K252a treatment suppressed early embryo development by inhibiting blastocyst cell numbers, and increasing blastocyst apoptosis. Our findings suggested that BDNF signaling plays important paracrine roles during blastocyst development by promoting the development of preimplantation embryos.

UI MeSH Term Description Entries
D009414 Nerve Growth Factors Factors which enhance the growth potentialities of sensory and sympathetic nerve cells. Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D010057 Oviducts Ducts that serve exclusively for the passage of eggs from the ovaries to the exterior of the body. In non-mammals, they are termed oviducts. In mammals, they are highly specialized and known as FALLOPIAN TUBES. Oviduct
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014599 Uterus The hollow thick-walled muscular organ in the female PELVIS. It consists of the fundus which is the site of EMBRYO IMPLANTATION and FETAL DEVELOPMENT. Beyond the isthmus at the perineal end of fundus, is CERVIX UTERI (the neck) opening into VAGINA. Beyond the isthmi at the upper abdominal end of fundus, are the FALLOPIAN TUBES. Fundus Uteri,Uteri,Uterine Cornua,Uterine Fundus,Uterus Cornua,Womb,Cornua, Uterine,Fundus Uterus,Fundus, Uterine,Uteri, Fundus,Wombs
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D019208 Brain-Derived Neurotrophic Factor A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994) BDNF,Brain Derived Neurotrophic Factor,Factor, Brain-Derived Neurotrophic,Neurotrophic Factor, Brain-Derived
D020813 Receptor, trkB A protein-tyrosine kinase receptor that is specific for BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN 3; neurotrophin 4 and neurotrophin 5. It is widely expressed in nervous tissue and plays a role in mediating the effects of neurotrophins on growth and differentiation of neuronal cells. BDNF Receptor,NTRK2 Receptor,Neurotrophic Factor, Brain-Derived, Receptor,trkB Receptor,Brain Derived Neurotrophic Factor Receptor,Neurotrophic Tyrosine Kinase Receptor Type 2,Receptor, Neurotrophic Tyrosine Kinase Type 2,trkB(gp145) Protein,Receptor, BDNF,Receptor, NTRK2

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