No conflicts of interest were declared.
Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance†
Article first published online: 18 JUL 2012
Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 228, Issue 3, pages 322–332, November 2012
How to Cite
Fraser, R., Whitley, G. S., Johnstone, A. P., Host, A. J., Sebire, N. J., Thilaganathan, B. and Cartwright, J. E. (2012), Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance. J. Pathol., 228: 322–332. doi: 10.1002/path.4057
- Issue published online: 12 OCT 2012
- Article first published online: 18 JUL 2012
- Accepted manuscript online: 31 MAY 2012 06:51AM EST
- Manuscript Accepted: 21 MAY 2012
- Manuscript Revised: 27 APR 2012
- Manuscript Received: 7 FEB 2012
- Re-use of this article is permitted in accordance with the Terms and Conditions set out at . [http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms]
- natural killer cell;
- spiral artery;
During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 9–14 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors. dNK cells from pregnancies with normal resistance indices could induce apoptotic changes in vascular smooth muscle and endothelial cells in vitro, events of importance in vessel remodelling, partly through Fas signalling. dNK cells isolated from high resistance index pregnancies failed to induce vascular apoptosis and secreted fewer pro-apoptotic factors. We have modelled the cellular interactions at the maternal-fetal interface and provide the first demonstration of a functional role for dNK cells in influencing vascular cells. A potential mechanism contributing to impaired vessel remodelling in pregnancies with a higher uterine artery resistance is presented. These findings may be informative in determining the cellular interactions contributing to the pathology of pregnancy disorders where remodelling is impaired, such as pre-eclampsia. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.