SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

First trimester placental endothelial cells from pregnancies with abnormal uterine artery Doppler are more sensitive to apoptotic stimuli.

Charolidi, N; Host, AJ; Ashton, S; Tryfonos, Z; Leslie, K; Thilaganathan, B; Cartwright, JE; Whitley, GS (2019) First trimester placental endothelial cells from pregnancies with abnormal uterine artery Doppler are more sensitive to apoptotic stimuli. Lab Invest, 99 (3). pp. 411-420. ISSN 1530-0307 https://doi.org/10.1038/s41374-018-0139-z
SGUL Authors: Cartwright, Judith Eleanor Whitley, Guy St John Charolidi, Nicoletta

[img]
Preview
PDF Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
[img]
Preview
PDF Accepted Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

Failure of the placental capillary network to develop normally is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). Although the symptoms are observed at term, the problem begins in the first trimester. However, investigations at this clinically relevant time are hindered by difficulties in identifying earlystage pregnancies that are at risk of developing FGR/PE. Using uterine artery Doppler ultrasound in the first trimester as a proxy measure of poor placentation, we have identified pregnancies at increased risk of developing early onset FGR/PE. Placental endothelial cells (PEC) isolated from pregnancies at increased risk of developing FGR/PE grew more slowly and their basal rate of apoptosis was significantly higher than that seen in the normal group. The pro-apoptotic stimulus, TNFα, induced apoptosis in cells from both groups but this was significantly greater in the high risk group. TNF receptor expression was unaffected. Inhibition of nitric oxide (NO) production significantly increased the sensitivity of cells from the normal pregnancies to TNFα but not in the high risk group establishing a functional role for NO in this system. In conclusion, first trimester PEC from pregnancies at increased risk of developing early onset FGR/PE were inherently more sensitive to apoptotic stimuli and this was functionally linked to the synthesis of NO. This may contribute to the poor placental vascular development seen in on going pregnancies.

Item Type: Article
Additional Information: © The Author(s) 2018. This article is published with open access Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: 1103 Clinical Sciences, Pathology
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: Lab Invest
ISSN: 1530-0307
Language: eng
Dates:
DateEvent
3 March 2019Published
5 October 2018Published Online
10 August 2018Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MR/M02184X/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
091550Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 30291324
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/110044
Publisher's version: https://doi.org/10.1038/s41374-018-0139-z

Actions (login required)

Edit Item Edit Item