PMID- 17880937 OWN - NLM STAT- MEDLINE DCOM- 20071203 LR - 20220331 IS - 1095-564X (Electronic) IS - 0012-1606 (Linking) VI - 311 IP - 1 DP - 2007 Nov 1 TI - Regulation of preimplantation embryo development by brain-derived neurotrophic factor. PG - 147-58 AB - 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. FAU - Kawamura, Kazuhiro AU - Kawamura K AD - Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita, 010-8543, Japan. kawamura@yf7.so-net.ne.jp FAU - Kawamura, Nanami AU - Kawamura N FAU - Fukuda, Jun AU - Fukuda J FAU - Kumagai, Jin AU - Kumagai J FAU - Hsueh, Aaron J W AU - Hsueh AJ FAU - Tanaka, Toshinobu AU - Tanaka T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070821 PL - United States TA - Dev Biol JT - Developmental biology JID - 0372762 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Embryo, Mammalian/*metabolism MH - Female MH - Mice MH - Nerve Growth Factors/metabolism MH - Oviducts/metabolism MH - Receptor, trkB/metabolism MH - Signal Transduction MH - Uterus/metabolism EDAT- 2007/09/21 09:00 MHDA- 2007/12/06 09:00 CRDT- 2007/09/21 09:00 PHST- 2007/06/15 00:00 [received] PHST- 2007/07/17 00:00 [revised] PHST- 2007/08/09 00:00 [accepted] PHST- 2007/09/21 09:00 [pubmed] PHST- 2007/12/06 09:00 [medline] PHST- 2007/09/21 09:00 [entrez] AID - S0012-1606(07)01271-7 [pii] AID - 10.1016/j.ydbio.2007.08.026 [doi] PST - ppublish SO - Dev Biol. 2007 Nov 1;311(1):147-58. doi: 10.1016/j.ydbio.2007.08.026. Epub 2007 Aug 21.