PMID- 11566754
OWN - NLM
STAT- MEDLINE
DCOM- 20011205
LR  - 20190513
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 65
IP  - 4
DP  - 2001 Oct
TI  - Regulation of human cytotrophoblast morphogenesis by hepatocyte growth 
      factor/scatter factor.
PG  - 1278-88
AB  - In vitro morphogenesis of epithelial cells to form tube-like structures is 
      regulated by hepatocyte growth factor-scatter factor (HGF/SF). The placenta is a 
      rich source of HGF/SF, and its absence in mice has been shown to lead to impaired 
      placental growth and embryonic death. There is no information in the literature 
      regarding in vitro morphogenesis of human cytotrophoblasts or the effect of 
      HGF/SF on this process. In this study, cytotrophoblasts were isolated from human 
      placentae obtained from all three trimesters of gestation and cultured on the 
      recombinant basement membrane matrix (Matrigel). Under these conditions, 
      cytotrophoblasts participated in morphogenetic events including formation of 
      spheroid-like structures, radial linear processes with branching, and invaded 
      Matrigel and formed large, tube-like structures. The presence of a developing 
      lumen was documented in the linear projections arising from spheroids and in the 
      tube-like structures by both confocal and transmission electron microscopy. 
      Immunohistochemistry was used to characterize the phenotype of the cells, and 
      staining with anti-cytokeratin and anti-E-cadherin antibodies confirmed the 
      presence of cytotrophoblasts in both the spheroids and tube-like structures. 
      Recombinant HGF (rHGF) significantly increased the invasive activity of 
      cytotrophoblasts isolated from the first and second (P < 0.001) and third 
      trimesters (P < 0.01). In addition, rHGF significantly increased the percentage 
      of spheroids with branching processes in the first and second trimesters (P < 
      0.05). Anti-HGF antibody inhibited both these effects in a dose-dependent manner, 
      indicating the specificity of the above findings. This study provides new 
      evidence indicating that HGF/SF regulates invasion and branching morphogenesis of 
      cytotrophoblasts throughout gestation, with maximum effects in the first and 
      second trimester. These findings may help to elucidate the importance of the 
      reduced expression of HGF/SF identified in placentae from women with preeclampsia 
      or intrauterine growth restriction and suggest that HGF/SF may serve as an 
      important candidate in therapeutic intervention strategies.
FAU - Dokras, A
AU  - Dokras A
AD  - Department of Obstetrics and Gynecology, The University of Iowa, Iowa City, Iowa 
      52240, USA. anuja-dokras@uiowa.edu
FAU - Gardner, L M
AU  - Gardner LM
FAU - Seftor, E A
AU  - Seftor EA
FAU - Hendrix, M J
AU  - Hendrix MJ
LA  - eng
GR  - 5K12HD00849/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Cadherins)
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (Recombinant Proteins)
RN  - 119978-18-6 (matrigel)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 68238-35-7 (Keratins)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Cadherins/analysis
MH  - Collagen
MH  - Culture Techniques
MH  - Drug Combinations
MH  - Female
MH  - Gestational Age
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Keratins/analysis
MH  - Laminin
MH  - Microscopy, Confocal
MH  - Microscopy, Electron
MH  - *Morphogenesis
MH  - Pregnancy
MH  - Proteoglycans
MH  - Recombinant Proteins/pharmacology
MH  - Trophoblasts/cytology/*physiology
EDAT- 2001/09/22 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/09/22 10:00
PHST- 2001/09/22 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/09/22 10:00 [entrez]
AID - 10.1095/biolreprod65.4.1278 [doi]
PST - ppublish
SO  - Biol Reprod. 2001 Oct;65(4):1278-88. doi: 10.1095/biolreprod65.4.1278.