Impaired Decidual Natural Killer Cell Regulation of Trophoblast Invasion and Vascular Remodelling in Pregnancies at Higher Risk of Pre-Eclampsia

Rupsha Fraser; Guy St J Whitley; Alan P Johnstone; Baskaran Thilaganathan; Judith E Cartwright

doi:10.1177/193371912011183s067

Abstract

Objectives: For successful pregnancy outcome, uterine spiral arteries are
remodelled from narrow, high resistance vessels into larger diameter, higher
flow vessels, providing sufficient oxygen and nutrients to support the developing
fetus. This remodelling process is deficient in pre-eclampsia (PE). Placental
trophoblast induce apoptosis in vascular cells lining the arteries and replace
them to create low resistance vessels. Decidual natural killer (dNK) cells
accumulate around spiral arteries and are present throughout the remodelling
process, but their role in remodelling has not been fully defined. In this study,
we investigated the effect of dNK cells on trophoblast motility and vascular
remodelling.
Methods: Uterine artery Doppler scanning was used to identify pregnancies
at low risk (25%) of developing PE. CD56+ dNK cells
were isolated from first trimester decidua. dNK cells or culture supernatants
(CS) were cultured with trophoblast, vascular smooth muscle cells (VSMC)
or endothelial cells (EC). Trophoblast motility (a component of invasion),
VSMC/EC apoptotic morphology, and integrity of EC tube-like structures
were examined by time-lapse microscopy. Apoptosis was confirmed by caspase
inhibition and detection of cleaved PARP by western blot analysis.
Results: Low risk dNK CS induced trophoblast to be more motile than high
risk dNK CS (pblocking antibody inhibited low risk dNK induced motility (prisk dNK cells significantly induced VSMC (papoptosis. High risk dNK cells failed to induce vascular cell apoptosis. EC
apoptosis induction was partly blocked by inhibiting FasL (phigh risk dNK cells secreted less FasL. Low risk dNK CS caused more
destabilisation of EC tube-like structures than high risk dNK CS (pBlocking TNF-α inhibited low risk dNK CS destabilisation of EC tube-like
structures (pConclusion: dNK cells affect trophoblast motility, induce vascular cell
apoptosis and destabilise EC tube-like structures. dNK cells from pregnancies
at higher risk of PE induce less trophoblast motility, fail to induce vascular
cell apoptosis and are less able to destabilise EC vessel-like structures.
These deficiencies may contribute to the aberrant invasion and spiral artery
remodelling seen in PE.

Original language	English
Pages (from-to)	272A
Number of pages	1
Journal	Reproductive Sciences
Volume	18
Issue number	Suppl 3
DOIs	https://doi.org/10.1177/193371912011183s067
Publication status	Published - 30 Dec 2011
Event	58th Annual Scientific Meeting of the Society for Gynecologic Investigation - Miami Beach, United States Duration: 16 Mar 2010 → 19 Mar 2010

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@article{fecdaa85d34e411fa6d43d5eae3721eb,

title = "Impaired Decidual Natural Killer Cell Regulation of Trophoblast Invasion and Vascular Remodelling in Pregnancies at Higher Risk of Pre-Eclampsia",

abstract = "Objectives: For successful pregnancy outcome, uterine spiral arteries are remodelled from narrow, high resistance vessels into larger diameter, higher flow vessels, providing sufficient oxygen and nutrients to support the developing fetus. This remodelling process is deficient in pre-eclampsia (PE). Placental trophoblast induce apoptosis in vascular cells lining the arteries and replace them to create low resistance vessels. Decidual natural killer (dNK) cells accumulate around spiral arteries and are present throughout the remodelling process, but their role in remodelling has not been fully defined. In this study, we investigated the effect of dNK cells on trophoblast motility and vascular remodelling. Methods: Uterine artery Doppler scanning was used to identify pregnancies at low risk (25\%) of developing PE. CD56+ dNK cells were isolated from first trimester decidua. dNK cells or culture supernatants (CS) were cultured with trophoblast, vascular smooth muscle cells (VSMC) or endothelial cells (EC). Trophoblast motility (a component of invasion), VSMC/EC apoptotic morphology, and integrity of EC tube-like structures were examined by time-lapse microscopy. Apoptosis was confirmed by caspase inhibition and detection of cleaved PARP by western blot analysis. Results: Low risk dNK CS induced trophoblast to be more motile than high risk dNK CS (pblocking antibody inhibited low risk dNK induced motility (prisk dNK cells significantly induced VSMC (papoptosis. High risk dNK cells failed to induce vascular cell apoptosis. EC apoptosis induction was partly blocked by inhibiting FasL (phigh risk dNK cells secreted less FasL. Low risk dNK CS caused more destabilisation of EC tube-like structures than high risk dNK CS (pBlocking TNF-α inhibited low risk dNK CS destabilisation of EC tube-like structures (pConclusion: dNK cells affect trophoblast motility, induce vascular cell apoptosis and destabilise EC tube-like structures. dNK cells from pregnancies at higher risk of PE induce less trophoblast motility, fail to induce vascular cell apoptosis and are less able to destabilise EC vessel-like structures. These deficiencies may contribute to the aberrant invasion and spiral artery remodelling seen in PE.",

author = "Rupsha Fraser and Whitley, \{Guy St J\} and Johnstone, \{Alan P\} and Baskaran Thilaganathan and Cartwright, \{Judith E\}",

year = "2011",

month = dec,

day = "30",

doi = "10.1177/193371912011183s067",

language = "English",

volume = "18",

pages = "272A",

journal = "Reproductive Sciences",

issn = "1933-7191",

publisher = "Springer Nature",

number = "Suppl 3",

note = "58th Annual Scientific Meeting of the Society for Gynecologic Investigation ; Conference date: 16-03-2010 Through 19-03-2010",

}

TY - JOUR

T1 - Impaired Decidual Natural Killer Cell Regulation of Trophoblast Invasion and Vascular Remodelling in Pregnancies at Higher Risk of Pre-Eclampsia

AU - Fraser, Rupsha

AU - Whitley, Guy St J

AU - Johnstone, Alan P

AU - Thilaganathan, Baskaran

AU - Cartwright, Judith E

PY - 2011/12/30

Y1 - 2011/12/30

N2 - Objectives: For successful pregnancy outcome, uterine spiral arteries are remodelled from narrow, high resistance vessels into larger diameter, higher flow vessels, providing sufficient oxygen and nutrients to support the developing fetus. This remodelling process is deficient in pre-eclampsia (PE). Placental trophoblast induce apoptosis in vascular cells lining the arteries and replace them to create low resistance vessels. Decidual natural killer (dNK) cells accumulate around spiral arteries and are present throughout the remodelling process, but their role in remodelling has not been fully defined. In this study, we investigated the effect of dNK cells on trophoblast motility and vascular remodelling. Methods: Uterine artery Doppler scanning was used to identify pregnancies at low risk (25%) of developing PE. CD56+ dNK cells were isolated from first trimester decidua. dNK cells or culture supernatants (CS) were cultured with trophoblast, vascular smooth muscle cells (VSMC) or endothelial cells (EC). Trophoblast motility (a component of invasion), VSMC/EC apoptotic morphology, and integrity of EC tube-like structures were examined by time-lapse microscopy. Apoptosis was confirmed by caspase inhibition and detection of cleaved PARP by western blot analysis. Results: Low risk dNK CS induced trophoblast to be more motile than high risk dNK CS (pblocking antibody inhibited low risk dNK induced motility (prisk dNK cells significantly induced VSMC (papoptosis. High risk dNK cells failed to induce vascular cell apoptosis. EC apoptosis induction was partly blocked by inhibiting FasL (phigh risk dNK cells secreted less FasL. Low risk dNK CS caused more destabilisation of EC tube-like structures than high risk dNK CS (pBlocking TNF-α inhibited low risk dNK CS destabilisation of EC tube-like structures (pConclusion: dNK cells affect trophoblast motility, induce vascular cell apoptosis and destabilise EC tube-like structures. dNK cells from pregnancies at higher risk of PE induce less trophoblast motility, fail to induce vascular cell apoptosis and are less able to destabilise EC vessel-like structures. These deficiencies may contribute to the aberrant invasion and spiral artery remodelling seen in PE.

AB - Objectives: For successful pregnancy outcome, uterine spiral arteries are remodelled from narrow, high resistance vessels into larger diameter, higher flow vessels, providing sufficient oxygen and nutrients to support the developing fetus. This remodelling process is deficient in pre-eclampsia (PE). Placental trophoblast induce apoptosis in vascular cells lining the arteries and replace them to create low resistance vessels. Decidual natural killer (dNK) cells accumulate around spiral arteries and are present throughout the remodelling process, but their role in remodelling has not been fully defined. In this study, we investigated the effect of dNK cells on trophoblast motility and vascular remodelling. Methods: Uterine artery Doppler scanning was used to identify pregnancies at low risk (25%) of developing PE. CD56+ dNK cells were isolated from first trimester decidua. dNK cells or culture supernatants (CS) were cultured with trophoblast, vascular smooth muscle cells (VSMC) or endothelial cells (EC). Trophoblast motility (a component of invasion), VSMC/EC apoptotic morphology, and integrity of EC tube-like structures were examined by time-lapse microscopy. Apoptosis was confirmed by caspase inhibition and detection of cleaved PARP by western blot analysis. Results: Low risk dNK CS induced trophoblast to be more motile than high risk dNK CS (pblocking antibody inhibited low risk dNK induced motility (prisk dNK cells significantly induced VSMC (papoptosis. High risk dNK cells failed to induce vascular cell apoptosis. EC apoptosis induction was partly blocked by inhibiting FasL (phigh risk dNK cells secreted less FasL. Low risk dNK CS caused more destabilisation of EC tube-like structures than high risk dNK CS (pBlocking TNF-α inhibited low risk dNK CS destabilisation of EC tube-like structures (pConclusion: dNK cells affect trophoblast motility, induce vascular cell apoptosis and destabilise EC tube-like structures. dNK cells from pregnancies at higher risk of PE induce less trophoblast motility, fail to induce vascular cell apoptosis and are less able to destabilise EC vessel-like structures. These deficiencies may contribute to the aberrant invasion and spiral artery remodelling seen in PE.

U2 - 10.1177/193371912011183s067

DO - 10.1177/193371912011183s067

M3 - Meeting abstract

SN - 1933-7191

VL - 18

SP - 272A

JO - Reproductive Sciences

JF - Reproductive Sciences

IS - Suppl 3

T2 - 58th Annual Scientific Meeting of the Society for Gynecologic Investigation

Y2 - 16 March 2010 through 19 March 2010

ER -

Impaired Decidual Natural Killer Cell Regulation of Trophoblast Invasion and Vascular Remodelling in Pregnancies at Higher Risk of Pre-Eclampsia

Abstract

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