Uterine natural killer cells initiate spiral artery remodeling in human pregnancy

Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are...

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Bibliographic Details
Published in:The FASEB journal Vol. 26; no. 12; p. 4876
Main Authors: Robson, Andrew, Harris, Lynda K, Innes, Barbara A, Lash, Gendie E, Aljunaidy, Mais M, Aplin, John D, Baker, Philip N, Robson, Stephen C, Bulmer, Judith N
Format: Journal Article
Language:English
Published: United States 01.12.2012
Subjects:
Angiopoietin-1 - metabolism
Angiopoietin-1 - pharmacology
Angiopoietin-2 - metabolism
Angiopoietin-2 - pharmacology
Cell Line
Cells, Cultured
Culture Media, Conditioned - metabolism
Culture Media, Conditioned - pharmacology
Decidua - cytology
Decidua - metabolism
Extracellular Matrix - drug effects
Extracellular Matrix - metabolism
Female
Humans
Immunohistochemistry
Interferon-gamma - metabolism
Interferon-gamma - pharmacology
Killer Cells, Natural - metabolism
Killer Cells, Natural - physiology
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Myometrium - cytology
Myometrium - metabolism
Placenta - cytology
Placenta - metabolism
Pregnancy
Tissue Culture Techniques
Trophoblasts - cytology
Trophoblasts - metabolism
Trophoblasts - physiology
Uterine Artery - cytology
Uterine Artery - drug effects
Uterine Artery - physiology
Uterus - blood supply
Uterus - cytology
Vascular Endothelial Growth Factor C - metabolism
Vascular Endothelial Growth Factor C - pharmacology
ISSN:1530-6860, 1530-6860
Online Access:Get more information
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Summary:Uterine spiral artery remodeling is required for successful human pregnancy; impaired remodeling is associated with pregnancy complications, including late miscarriage, preeclampsia, and fetal growth restriction. The molecular triggers of remodeling are not known, but it is now clear that there are "trophoblast-independent" and "trophoblast-dependent" stages. Uterine natural killer (uNK) cells are abundant in decidualized endometrium in early pregnancy; they surround spiral arteries and secrete a range of angiogenic growth factors. We hypothesized that uNK cells mediate the initial stages of spiral artery remodeling. uNK cells and extravillous trophoblast (EVT) cells were isolated from early pregnancy decidua and placenta. Chorionic plate arteries from full-term placentas and spiral arteries from nonpregnant myometrium were cultured with angiogenic growth factors or conditioned medium (CM) from uNK cells or EVT or uNK cell/EVT cocultures. In both vessel models, uNK cell CM induced disruption of vascular smooth muscle cells (VSMCs) and breakdown of extracellular matrix components. Angiopoietin (Ang)-1, Ang-2, interferon-γ, and VEGF-C also disrupted VSMC integrity with an Ang-2 inhibitor abrogating the effect of uNK cell CM. These results provide compelling evidence that uNK cells contribute to the early stages of spiral artery remodeling; failure of this process could contribute to pregnancy pathology.
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ISSN:1530-6860
1530-6860
DOI:10.1096/fj.12-210310