Download Placental M-CSF, GM-CSF and G-CSF alterations in

Placental M-CSF, GM-CSF and G-CSF
alterations in Small for Gestational Age
infants.
U. Rajesh ‫٭‬, A.L. Seager, R.H. Jones, T.V. Macfarlane,B. Manshian,
M. Moller, G. Morgan, C.A. Thornton.
Singleton Hospital ,Swansea.
Institute of Life Science,
School of Medicine,
Swansea University, Swansea.
‫٭‬
SGA

Physiologic adaptive response to various stimuli
acting to limit

50-70% of fetuses with a birth weight below the
10th centile for gestational age are constitutionally
small (Ott WJ 1988, Wilcox AJ,1983).

Heterogenous group of fetuses that have failed to
achieve their growth potential-IUGR

Fetuses that are constitutionallly small throughout
pregnancy-SFD
Background
Cytokines provide an important communication
system in coordinating immune and inflammatory
responses.
 Several
cytokines have been identified in
placenta and/or uterus.
A number of colony stimulating factors (CSFs),
which are named for their major target cells,
 Granulocyte -G-CSF
 Granulocyte-macrophage- GM-CSF
 Macrophage-MCSF

Background

M-CSF -Macrophage Colony Stimulating FactorIt is a Haematopoietic cytokine mediating
 placental growth,
 development and proliferation of myeloid
haematopoietic cells.

M-CSF is secreted by uterine gland cells, and the
levels increased in the first few days of pregnancy,
with receptor present on invasive trophoblast cells.
Pollard et al., Nature. 1987.
Background

There is evidence for expression of M-CSF, GMCSF and G-CSF in the Feto-Maternal interface.
Ringler,1989, Robertson 1990
 Few
studies have shown alterations in levels
of M-CSF, GM CSF in placental tissue in
intrauterine disease.
Hayashi 1996 &1998, Stallmach 1995.
Objectives

To evaluate whether M-CSF, GM-CSF and G-CSF levels
in placentas of SGA (Small for Gestational Age) differ
from AGA (Appropriate for Gestational Age) controls.

To correlate alterations in these essential cytokines in
placentas of SGA infants while attempting to classify
clinical phenotypes of SGA.

Understand placental role in pathophysiology of SGA
better.
Methods




Definitions of SGA
LREC approval
Consent
Recruitment
IUGR
 Constitutionally small for dates (SFD)
 Controls (AGA)

Fundal Ht
Customised growth chart
Methods



Cord Blood &Placenta Collection
Placental Explant culture
Sandwich ELISA
 Quantikine kit (R&D Systems, UK) used
 Quantify cytokines in stored supernatants
 Cord blood serum analysis
• SPSS Version 13

Mann Whitney U test
Results
n=65
14=Term SFD
12=Term IUGR
5=Preterm IUGR
32=Term Controls
2=Preterm Controls
Results
Parameters
IUGR
SFD
Controls
n=17
n=14
n=34
Maternal Age
26
29
28
Parity- Primi- gravidas
10
5
12
9
8
19
8
5
15
37
38.5
39
Mean Birth Weight (g)
2167
2720
3230
Head Circumference
33
34
34
Placenta weight
442
527
657
SCBU admission
7
0
2
Mode of Delivery- Vaginal
C. Section
Gestation (Wks)
TERM
G-CSF (pg/0.2g tissue /ml)
GM-CSF(pg/0.2g tissue/ml)
Results
IUGR
SFD
Control
IUGR
SFD
Control
Placental M-CSF(pg/0.2g tissue/ml)
Results
p=0.005
P=0.090
IUGR
SFD
CONTROL
Serum M-CSF(pg/ml)
Results
Conclusions

First report distinguishing clinical phenotypes of
SGA (IUGR and SFD) and correlating with
cytokine alterations.

The reduced M-CSF in placenta of IUGR and SFD
infants probably reflects poor placental
development and function.

Increased M-CSF in maternal serum has been
noted in IUGR pregnancies.
 Does Maternal M-CSF down regulate the
placental and fetal production of M-CSF?
Future directions

Study maternal blood along with cord blood
and placenta to correlate changes

Redistribution Doppler studies to identify
severe IUGR and correlate findings.

Further study of amniotic fluid, placenta, cord
blood &maternal serum for cytokine changes.
Therapeutic implications
Methods of diagnosing and treating pre eclampsia
Methods are provided for the diagnosis and treatment of patients
with increased risk of gestational hypertension or pre eclampsia.
The methods involve measuring serum M-CSF levels,
and administration of M-CSF.
MUMBLES
ILS
Thank you
cds
GM-CSF
Group
Mean(pg/ml)
G-CSF
M-CSF
Mean(pg/ml)
Std.Deviation
Mean(pg/ml)
Std.Deviation
Std.Deviation
1
49.69
52.73
22968.3
16305.58
579.95
351.12
2
49.02
51.2
24.659.8
26863.4
774.96
319.85
3
38.98
27.38
24177.4
22310.1
1455.63
1349.22
Extra stuff
GM-CSF
Group
Mean(pg/ml
)
Std.Devia
tion
1
49.69
52.73
2
49.02
51.2
3
38.98
27.38
G-CSF
M-CSF
Mean(pg/ml
)
Std.Deviatio
n
Mean(pg/ml
)
Std.Deviatio
n
22968.3
16305.58
579.95
351.12
26863.4
774.96
319.85
22310.1
1455.63
1349.22
24.659.8
24177.4
Background

In humans, the expression and localization of mRNA for M-CSF
have been demonstrated in mesenchymal cells of the chorionic
villous stroma, particularly in cytotrophoblasts lining the villous core
and in the cytotrophoblastic core in the first trimester; in villous
mesenchymal cells in the second trimester; and in cells lining the
villous vessels in the third trimester.



Kanazaki et al., Human Reprod., 7:563-567 (1992);
Daiter et al., J. Clin. Endocrinol. Metab. 74:850-858 (1992).
Circulating levels of macrophage M-CSF during pregnancy are also
higher than those of non-pregnant women. Yong et al., Blood,
180:2897-2902 (1992).