PMID- 19372195
OWN - NLM
STAT- MEDLINE
DCOM- 20090805
LR  - 20220331
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 8
DP  - 2009 Aug
TI  - Brain-derived neurotrophic factor promotes implantation and subsequent placental 
      development by stimulating trophoblast cell growth and survival.
PG  - 3774-82
LID - 10.1210/en.2009-0213 [doi]
AB  - Successful implantation of the blastocyst and subsequent placental development is 
      essential for reproduction. Expression of brain-derived neurotrophic factor 
      (BDNF) and neurotrophin-4/5, together with their receptor, tyrosine kinase B 
      (TrkB), in trophectoderm cells of blastocyst suggests their potential roles in 
      implantation and placental development. Here we demonstrated that treatment with 
      BDNF promoted blastocyst outgrowth, but not adhesion, in vitro and increased 
      levels of the cell invasion marker matrix metalloproteinase-9 in cultured 
      blastocysts through the phosphatidylinositol 3-kinase pathway. After 
      implantation, BDNF and neurotrophin-4/5 proteins as well as TrkB were expressed 
      in trophoblast cells and placentas during different stages of pregnancy. Both 
      TrkB and its ligands were also expressed in decidual cells. Treatment of cultured 
      trophoblast cells with the TrkB ectodomain, or a Trk receptor inhibitor K252a, 
      suppressed cell growth as reflected by decreased proliferation and increased 
      apoptosis, whereas an inactive plasma membrane nonpermeable K252b was 
      ineffective. Studies using the specific inhibitors also indicated the importance 
      of the phosphatidylinositol 3-kinase/Akt pathway in mediating the action of TrkB 
      ligands. In vivo studies in pregnant mice further demonstrated that treatment 
      with K252a, but not K252b, suppressed placental development accompanied by 
      increases in trophoblast cell apoptosis and decreases in placental labyrinth zone 
      at midgestation. In vivo K252a treatment also decreased fetal weight at late 
      gestational stages. Our findings suggested important autocrine/paracrine roles of 
      the BDNF/TrkB signaling system during implantation, subsequent placental 
      development, and fetal growth by increasing trophoblast cell growth and survival.
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 - Sato, Wataru
AU  - Sato W
FAU - Fukuda, Jun
AU  - Fukuda J
FAU - Kumagai, Jin
AU  - Kumagai J
FAU - Tanaka, Toshinobu
AU  - Tanaka T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090416
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 145172-44-7 (neurotrophin 5)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Blastocyst/cytology/drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Adhesion/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Embryo Implantation/*drug effects
MH  - Female
MH  - Humans
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Nerve Growth Factors/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Placenta/cytology/drug effects/metabolism
MH  - Placentation/*drug effects
MH  - Pregnancy
MH  - Receptor, trkB/metabolism
MH  - Trophoblasts/cytology/*drug effects/metabolism
EDAT- 2009/04/18 09:00
MHDA- 2009/08/06 09:00
CRDT- 2009/04/18 09:00
PHST- 2009/04/18 09:00 [entrez]
PHST- 2009/04/18 09:00 [pubmed]
PHST- 2009/08/06 09:00 [medline]
AID - en.2009-0213 [pii]
AID - 10.1210/en.2009-0213 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Aug;150(8):3774-82. doi: 10.1210/en.2009-0213. Epub 2009 Apr 
      16.