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Decidual natural killer cell interactions with trophoblasts are impaired in pregnancies at increased risk of preeclampsia.

Wallace, AE; Host, AJ; Whitley, GS; Cartwright, JE (2013) Decidual natural killer cell interactions with trophoblasts are impaired in pregnancies at increased risk of preeclampsia. Am J Pathol, 183 (6). pp. 1853-1861. ISSN 1525-2191 https://doi.org/10.1016/j.ajpath.2013.08.023
SGUL Authors: Cartwright, Judith Eleanor Wallace, Alison Elizabeth Whitley, Guy St John Host, Amanda

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Abstract

Transformation of the uterine spiral arteries (SAs) during pregnancy is critical to support the developing fetus, and is impaired in some pregnancy disorders, including preeclampsia. Decidual natural killer (dNK) cells play a role in SA remodeling, although their interactions with fetal trophoblast remain unclear. A uterine artery Doppler resistance index (RI) in the first trimester of pregnancy can be used as a proxy measure of the extent of SA remodeling; we have used this technique to characterize dNK cells from pregnancies with normal (normal RI) and impaired (high RI) SA remodeling, which display least and highest risk of developing preeclampsia, respectively. We examined the impact of dNK cell secreted factors on trophoblast motility, chemoattraction, and signaling pathways to determine the contribution of dNK cells to SA transformation. We demonstrated that the chemoattraction of the trophoblast by dNK cells is impaired in pregnancies with high RI, as is the ability to induce trophoblast outgrowth from placental villous explants. These processes are dependent on activation of the extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase-Akt signaling pathways, which were altered in trophoblasts incubated with secreted factors from dNK cells from high RI pregnancies. Therefore, by characterizing pregnancies using uterine artery Doppler RI before dNK cell isolation, we have identified that impaired dNK-trophoblast interactions may lead to poor placentation. These findings have implications for pregnancy pathological conditions, such as preeclampsia.

Item Type: Article
Additional Information: Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0)
Keywords: Adult, Chemotaxis, Decidua, Female, Humans, Killer Cells, Natural, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Phosphatidylinositol 3-Kinases, Pre-Eclampsia, Pregnancy, Pregnancy Proteins, Proto-Oncogene Proteins c-akt, Risk Factors, Trophoblasts, Decidua, Killer Cells, Natural, Trophoblasts, Humans, Pre-Eclampsia, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Pregnancy Proteins, Risk Factors, Chemotaxis, MAP Kinase Signaling System, Pregnancy, Adult, Female, Proto-Oncogene Proteins c-akt, Phosphatidylinositol 3-Kinases, Science & Technology, Life Sciences & Biomedicine, Pathology, PATHOLOGY, UTERINE ARTERY DOPPLER, ACTIVATED PROTEIN-KINASES, GROWTH-FACTOR, NK CELLS, EXTRAVILLOUS TROPHOBLASTS, 1ST TRIMESTER, GESTATIONAL-AGE, PLACENTAL BED, NITRIC-OXIDE, INVASION, Pathology, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: Am J Pathol
ISSN: 1525-2191
Language: eng
Dates:
DateEvent
December 2013Published
6 October 2013Published Online
22 August 2013Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
091550Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 24103555
Web of Science ID: WOS:000327829000016
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107546
Publisher's version: https://doi.org/10.1016/j.ajpath.2013.08.023

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