| A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. | |
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MedLine Citation:
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PMID: 21693515 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 138 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-06-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 2987-98 Citation Subset: IM |
Affiliation:
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Center for Reproductive Sciences, University of California, San Francisco, CA 94143, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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