SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 166A

166A

Reproductive Sciences Vol. 25, Supplement 1, March 2018

CONCLUSION: RA and cAMP treatments both downregulate sFlt1
production in DSCs. Lack of induction in decidualization markers and
the consistent reduction of sFlt1 in the decidualization defective cell line
suggests sFlt1 modulation by RA involves signaling pathways distinct
from decidualization induced by cAMP. We conclude that decidualization
of DSC is not a requirement for RA mediated inhibition of sFlt1.

T-169
The Effect of Low-Dose Aspirin on Placental Growth Factor
Concentration in a High-Risk PREDO Cohort. Katja Murtoniemi†,3
Tero Vahlberg, 6 Esa Hämäläinen, 7 Eero Kajantie, 1 Anu-Katriina
Pesonen,3 Katri Räikkönen,3 Pekka Taipale,2 Pia Maria Villa*,4 Hannele
Laivuori*.3,5 1National Institute for Health and Welfare, Helsinki, Finland;
2
Terveystalo Oy, Kuopio, Finland; 3University of Helsinki, Helsinki,
Finland; 4University of Helsinki and Helsinki University Hospital,
Helsinki, Finland; 5University of Tampere and Tampere University
Hospital, Tampere, Finland; 6University of Turku, Turku, Finland; 7VITATerveyspalvelut Oy, Helsinki, Finland.
INTRODUCTION: Placental growth factor (PlGF) is a promising
biomarker for preeclampsia (PE). Low-dose acetylsalicylic acid (ASA,
aspirin) started at 12-16 weeks of gestation reduces the risk of PE. We
studied the effect of ASA 100mg/day, started at 11-14 weeks of gestation,
on serum PlGF concentrations in a prospective cohort of women with
clinical risk factors for PE.
METHODS: Women who had bilateral second-degree diastolic notch
in Doppler ultrasound measurement of uterine arteries at 11-14 weeks of
gestation were randomized to the placebo-controlled ASA trial (Placebo
group N=61 and ASA group N=61). Blood samples were collected at
11-14, at 18-20 and at 26-28 weeks of gestation from 454 women. PlGF
concentrations were determined with time-resolved immunofluorometric
assay AutoDelfia (PerkinElmer, Wallac, Turku). Study cohort was divided
into 7 groups: Group 1: low-risk women (N=101), group 2: risk-women
who did not develop PE (N=163), group 3: risk-women who developed
PE (N =23), group 4: risk-women who had placebo treatment and did
not develop PE (N=51), group 5: risk-women who had placebo treatment
and developed PE (N=11), group 6: risk-women who had ASA treatment
and did not develop PE (N=55) and group 7: risk-women who had ASA
treatment and developed PE (N=6). The repeated measures analysis of
variance (ANOVA) was used to analyze differences in serum PlGF levels
between the groups. The model included the main effects of time, group
and the interaction effect time×group. Logarithmic transformations of
PlGF values were used in these analyses.
RESULTS: There were no differences in serum PlGF levels between
groups 1, 2, 4, 6 and 7, at any of the three trimesters (p=0.15). The
increase in serum PlGF levels during pregnancy was significantly lower
in group 3 and group 5 compared to the other groups (time×group effect,
p<0.001) (Figure).
CONCLUSION: Our finding suggests an association between low-dose
ASA and higher increase in serum PlGF concentration. Larger studies
are needed to clarify if ASA reduces risk for PE by increasing serum
PlGF levels.
*Figure(s) will be available online.

T-170
Maternal Adaptation to Twin Pregnancy. Maria C Adank†, Sarah
Schalekamp-Timmermans, Eric AP Steegers. Erasmus Medical Center,
Rotterdam, Netherlands.
INTRODUCTION: Twin pregnancy poses a risk for gestational
hypertensive disorders (GHD) such as preeclampsia (PE). As PE is
associated with cardiovascular disease (CVD) later in life, the aim of this
study was to investigate (long term) maternal hemodynamic adaptation
in women with a twin pregnancy and the maternal cardiovascular profile
after a twin pregnancy.
METHODS: Ninety women with a twin pregnancy were compared
with 7868 women carrying a singleton. All women participated in
the prospective cohort study Generation R. In pregnancy we obtained
information on: soluble fms-like tyrosine kinase-1 (sFLT-1), placental
growth factor (PlGF), first, second and third trimester systolic (SBP) and

Scientific Abstracts

diastolic blood pressure (DBP), the occurrence of PE and the resistance
index of the uterine artery (RI-UtA). Six years after the index pregnancy
SBP and DBP, and peak wave velocity were measured, and we performed
echocardiographic measurements including left ventricular mass, aortic
root diameter, left atrial diameter and fractional shortening. Retinal
arteriolar and venular calibers, representing maternal microvasculature
after pregnancy were measured in the left eye from digitized retinal
photographs. Missing values in covariates were imputed using multiple
imputation procedures. Associations between singleton and twin
pregnancies were assessed through linear and logistic regression analyses.
RESULTS: First and second trimester sFLT-1 and PlGF concentrations
were higher in women with twin pregnancies compared to women with
singleton pregnancies. In third trimester, women with twin pregnancies
had a lower RI-UtA (-0.04 (95% confidence interval (CI) -0.07; -0.01))
and a higher DBP (2.59 mmHg (95% CI 0.28; 4.90)). Women with a
twin pregnancy had a substantially higher risk for the development of
PE (OR 3.5 (95% CI 1.70; 7.51)). Six years after pregnancy, we did not
observe differences in the cardiovascular profile (microvasculature and
macrovasculature) of women with a previous twin pregnancy compared
to women with a previous singleton pregnancy.
CONCLUSION: Women with a twin pregnancy show hemodynamic
differences during pregnancy compared to women with a singleton
pregnancy. Moreover, they show a 3.5 fold increased risk for developing
preeclampsia. Six years after pregnancy, hemodynamic differences seem
to resolve with no altered status of the micro- and macrovasculature. Twin
pregnancies show no direct influence of PE or specific pre-pregnancy risk
factors for CVD in later life.

T-171
c-Src Kinase Inhibition Did Not Rescue VEGF-Induced Junctional
Disruption in Glomerular Endothelial Cells. Kenna R Degner†, Cynthia
E Bird†, Ian M Bird*, Dinesh M Shah*. University of Wisconsin-Madison
School of Medicine and Public Health, Madison, WI, United States.
INTRODUCTION: The mechanisms responsible for driving renal
dysfunction in preeclampsia (PE) remain poorly understood making
therapeutic intervention difficult. In PE, glomerular endothelial cell
(GEnC) injury leads to a breakdown of barrier function and proteinuria.
We have previously shown increased glomerular VEGF staining in a PE
mouse model, also observed in PE patients, and VEGF driven disruption
of cell junctions in vitro; however, little research has explored VEGF
as a contributor to GEnC injury in PE. We propose VEGF contributes
to loss in GEnC barrier function by disrupting junctional proteins. In
vascular endothelial cells, Src inhibition protects against junctional protein
internalization and barrier leakage, but this has not been tested in GEnCs.
We hypothesized that c-Src kinase inhibition in GEnC will protect against
VEGF-mediated GEnC junctional protein breakdown.
METHODS: VE-cadherin and ZO-1 expression and localization was
examined in GEnCs using standard western blotting and fluorescent
immunocytochemistry protocols. Cells were treated with VEGF, PP2,
or PP2 and VEGF and collected at 6 and 21 hours post treatment. We
examined changes in cellular resistance using the ECIS system. GEnCs
were treated with inhibitors PP2 (src), SKI-1 (src), U0126 (ERK1/2)
and SB203580 (p38) for 24 hours. Follow up experiments included
pretreatment with inhibitors followed by VEGF.
RESULTS: VE-cadherin and ZO-1 expression did not differ between
treatments at 6 or 21 hours. Localization at the cell membrane trended
lower in VEGF and PP2+VEGF treated groups at 6 hours and higher at 21
hours, but was not significant. PP2 and SKI reduced GEnC resistance at 6
hours (p<0.001) by ~20%, but did not differ from control by 21 hours. Src
inhibitor pretreatment followed by VEGF induced rapid loss in resistance
of ~25-30% and did not return to control levels (p<0.001). U0126 and
SB203580 treatment alone improved barrier function by 10-15% at 6 and
21 hours (p<0.002). VEGF combined treatments were also improved at 6
hours (p<0.001), but not different from control by 21 hours.
CONCLUSION: c-Src kinase inhibition in GEnC did not protect against
long-term VEGF-mediated loss in barrier function. Preliminary data show

Table of Contents for the Digital Edition of SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018