Document Detail

A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia.
MedLine Citation:
PMID:  21693515     Owner:  NLM     Status:  MEDLINE    
Placental trophoblasts (TBs) invade and remodel uterine vessels with an arterial bias. This process, which involves vascular mimicry, re-routes maternal blood to the placenta, but fails in pre-eclampsia. We investigated Notch family members in both contexts, as they play important roles in arterial differentiation/function. Immunoanalyses of tissue sections showed step-wise modulation of Notch receptors/ligands during human TB invasion. Inhibition of Notch signaling reduced invasion of cultured human TBs and expression of the arterial marker EFNB2. In mouse placentas, Notch activity was highest in endovascular TBs. Conditional deletion of Notch2, the only receptor upregulated during mouse TB invasion, reduced arterial invasion, the size of maternal blood canals by 30-40% and placental perfusion by 23%. By E11.5, there was litter-wide lethality in proportion to the number of mutant offspring. In pre-eclampsia, expression of the Notch ligand JAG1 was absent in perivascular and endovascular TBs. We conclude that Notch signaling is crucial for TB vascular invasion.
Nathan M Hunkapiller; Malgorzata Gasperowicz; Mirhan Kapidzic; Vicki Plaks; Emin Maltepe; Jan Kitajewski; Jay C Cross; Susan J Fisher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-22     Completed Date:  2011-09-09     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  2987-98     Citation Subset:  IM    
Center for Reproductive Sciences, University of California-San Francisco, CA 94143, USA.
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MeSH Terms
Arteries / growth & development
Calcium-Binding Proteins / metabolism
DNA Primers / genetics
Ephrin-B2 / metabolism
Fluorescent Antibody Technique
Gene Deletion
In Situ Hybridization
In Situ Nick-End Labeling
Intercellular Signaling Peptides and Proteins / metabolism
Membrane Proteins / metabolism
Placental Circulation / physiology*
Pre-Eclampsia / physiopathology*
Receptors, Notch / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / physiology*
Trophoblasts / metabolism,  physiology*
Uterus / blood supply*
Grant Support
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/DNA Primers; 0/Ephrin-B2; 0/Intercellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Receptors, Notch; 134324-36-0/Serrate proteins

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