SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 169A

Scientific Abstracts

T-179
Pregnancy Outcomes and Vascular Function in Lectin-Like Oxidized
LDL Receptor-1 Knockout Mice. Floor Spaans†,2,3 Jude S Morton,2,3
Raven Kirschenman,2,3 Tatsuya Sawamura,1 Sandra T Davidge*.2,3
1
Shinshu University, Matsumoto, Japan; 2University of Alberta, Edmonton,
AB, Canada; 3Women and Children's Health Research Institute,
Edmonton, AB, Canada.
INTRODUCTION: The development of hypertension and proteinuria in
preeclampsia (PE) is thought to be due to maternal systemic endothelial
dysfunction. The lectin-like oxidized LDL receptor-1 (LOX-1) is a multiligand scavenger receptor that is associated with vascular dysfunction.
We have previously shown that LOX-1 expression is increased in women
with PE, and that PE plasma factors disturbed vascular function via
LOX-1. However, the exact role of LOX-1 in contributing to vascular
maladaptations to pregnancy is unknown. Thus, to further investigate a
role for LOX-1 in pathological pregnancies, we propose to use genetically
modified LOX-1 deficient (knockout; KO) mice. We hypothesize that an
absence of the LOX-1 receptor would improve vascular function and
benefit pregnancy outcomes.
METHODS: C57BL/6 mice (WT; n=7-15) and LOX-1 KO mice (n=816) were sacrificed at the end of pregnancy on gestational day 18 (term =
day 19). Fetal and placental weights were collected. Uterine arteries were
obtained and isolated vessels were incubated overnight in physiological salt
solution. Using wire myography, endothelium-dependent (methylcholine;
MCh) vasodilation (in the presence or absence of L-NAME, a pan nitric
oxide synthase inhibitor), endothelium-independent vasodilation (sodium
nitroprusside; SNP) and high potassium physiological salt solution (KPSS)
mediated vasoconstriction responses were measured.
RESULTS: No differences in placental or fetal weights were observed
between WT and LOX-1KO mice, however, litter size was significantly
increased in LOX-1KO mice compared to WT mice (WT 7(2-10) vs. LOX1KO 9(7-10); p=0.003). Uterine arteries from LOX-1KO mice were less
sensitive to MCh than arteries from WT mice (pEC50: WT 7.4±0.06 vs.
LOX-1KO 7.1±0.08; p=0.01). Conversely, the nitric oxide contribution
to MCh-induced vasodilation was increased in LOX-1KO mice compared
to WT mice (delta AUC: WT 54.8±11.7 vs. LOX-1KO 146.4±34.9;
p=0.02). No changes were observed in SNP-induced vasodilation or
KPSS-mediated vasoconstriction.
CONCLUSION: Mice that do not express the LOX-1 receptor show
an improved pregnancy outcome, while also displaying a shift in the
mechanisms of endothelium-dependent vasodilation. This supports our
hypothesis that LOX-1 could play a role in the development of pregnancy
complications and indicate that the presence of the LOX-1 receptor
may be detrimental for pregnancy. The exact mechanisms, and whether
the vascular adaptations in LOX-1KO mice contribute to the improved
pregnancy outcome, remain to be further investigated. These data increase
our understanding of endothelial dysfunction in PE and contribute to the
development of novel treatment strategies in the future.

169A

T-180
Increased Leptin Receptor Expression in Human Placental Villous
Macrophages and Endothelial Cells in Preeclampsia Contributes to
Leptin-Induced Placental IL-6 Production. Chinedu Nwabuobi†,2 Sefa
Arlier,1 Frederick Schatz,2 Charles J Lockwood*,2 Umit A Kayisli.2 1Adana
Numune Training and Research Hospital, Adana, Turkey; 2University of
South Florida, Morsani College of Medicine, Tampa, FL, United States.
INTRODUCTION: Leptin, an adipocyte-secreted hormone, binds
to leptin receptor (LEPR) to centrally regulate body weight, and also
functions as a cytokine regulator of diverse physiological processes such
as immune response and angiogenesis. In preeclampsia (PE), immune
maladaptation contributes to impaired trophoblast invasion and incomplete
transformation of the spiral arteries. Mounting evidence suggests an
association between increased serum and placental leptin levels and PE,
as well as between serum and decidual interleukin 6 (IL-6) levels and PE.
We sought to further investigate expression of LEPR and its correlation
with IL-6 expression in placental villi in normal vs. PE.
METHODS: Placental paraffin sections (5-μm) obtained from
gestational age (GA) matched normal (n=7) and PE (n=8) pregnancies
were immunostained for LEPR or IL-6 and evaluated by a histologic
scoring (HSCORE) system. Statistical analysis used parametric and
non-parametric tests and a p value < 0.05 was considered significant.
RESULTS: Analysis of immunostained slides revealed that LEPR and
IL-6 immunoreactivity is present in both placental villous macrophages
[Hofbauer cells (HC)] and endothelial cells. In PE, HC and endothelial
cells displayed moderate immunoreactivity for LEPR expression, though
statistically significantly higher when compared to normal specimen (HC
p=0.002; endothelial cell p=0.001). Moreover, in PE specimens, IL-6
expression in endothelial cells was similar to that in normal placenta, while
HC displayed significantly higher immunoreactivity for IL-6 expression.
CONCLUSION: Decidua has been shown to be a source of IL-6 secretion
while fetal macrophages are not known to release IL-6. This study
identifies, higher levels of LEPR and IL-6 co-expressions in HC from
PE placenta, suggesting that induction of IL-6 secretion by LEPR-leptin
interaction in fetal macrophages (HCs) may contribute to PE-associated
inflammation. Further study will be needed to define the importance of
this relationship.
*Figure(s) will be available online.

T-181
Blood Pressure Profile One Year after Severe Pre-Eclampsia. Laura
Benschop†, Johannes J Duvekot*, Jorie Versmissen*, Valeska van
Broekhoven†, Eric AP Steegers*, Jeanine E Roeters van Lennep*.
Erasmus Medical Center, Rotterdam, Netherlands.
INTRODUCTION: Pre-eclampsia increases the long-term risk
of cardiovascular disease (CVD), possibly through occurrence of
hypertension after delivery. Masked hypertension, night-time hypertension
and an adverse dipping pattern of systolic night-to-day blood pressure
(BP) ratio are risk factors of CVD, which are often unnoticed and can
only be detected with ambulatory blood pressure monitoring (ABPM).
The objective of this study was to determine hypertension rate and 24hour BP pattern with ABPM and office BP measurements in women one
year after severe pre-eclampsia.
METHODS: This is a retrospective cohort study. As part of a followup program after severe pre-eclampsia 200 women underwent ABPM
and an office BP measurement one year after delivery (95% Confidence
Interval [CI] 9-15 months). We calculated hypertension rate (sustained
hypertension, masked hypertension and white-coat hypertension [WCH])
and systolic night-to-day BP ratio dipping pattern. Medical files and
questionnaires provided information on pre-existing hypertension and
antihypertensive treatment.
RESULTS: One year after delivery, 42.5% of women had some form of
hypertension (sustained hypertension, masked hypertension or WCH)
based on ABPM. Masked hypertension was most common (17.5%),
followed by sustained hypertension (15.5%) and WCH (9.5%). With
sheer office BP measurement only 25.0% of women would have been
diagnosed hypertensive. Forty-six percent of women a disadvantageous
systolic night-to-day BP ratio dipping pattern.

Thursday Posters

the pathways that are dysregulated in PE. Multiple testing correction
was performed using false discovery rate (FDR) adjustment in all data
analyses as appropriate. Changes in genes of interest were confirmed
using RT-qPCR.
RESULTS: A total of 1178 differentially expressed (FDR P-value<0.01,
fold change>|5|) genes were identified in PE vs. NT P0-HUVECs.
Reactome pathway enrichment analysis showed that the "Ion channel
transport", "Integrin cell surface interactions" and "Cellular responses
to stress" pathways were dysregulated in PE P0-HUVECs. In addition,
Ingenuity Pathway analysis revealed that many key endothelial functionassociated pathways including "PI3K/AKT signaling", "FGF signaling",
"VEGF signaling", "Cytokine signaling", and "HIFα signaling" were
dysregulated in PE P0-HUVECs.
CONCLUSION: PE dysregulates a large number of important
genes associated with endothelial function in fetal endothelial cells.
These differentially expressed genes in fetal endothelial cells could
serve as biomarkers for fetal endothelial dysfunctions and increased
risk of cardiovascular disorders in PE-offspring later in life. [AHA
17POST33670283, NIH HD38843 and HL117341]

Reproductive Sciences Vol. 25, Supplement 1, March 2018

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