SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 81A

Scientific Abstracts

increased concentrations of TNFa, IL8, and MCP1 at 27 weeks GA. The
concentration of IL10 was significantly negatively correlated with the
amount of walking reported by participants (ρ=-0.264).
CONCLUSION: Our results warrant further investigation of IL10 as
a predictive biomarker of SPTL. Low intensity exercise may have a
protective effect against SPTL through IL10-mediated pathways by
improving the balance between pro- and anti-inflammatory cytokines.
Asymptomatic pregnant women should be encouraged to partake in low
intensity exercise throughout pregnancy to reduce risk of SPTL.

O-072

O-073
Cardiovascular Risk Assessment and Follow-Up of Women after
Hypertensive Disorders of Pregnancy. Rachel A Gladstone†, Jessica
Pudwell, Graeme N Smith*. Queen's University, Kingston, ON, Canada.
INTRODUCTION: Hypertensive disorders of pregnancy are associated
with an increased risk of cardiovascular disease (CVD) in women and
serve as some of the earliest clinical indicators of CVD risk. This study
examines the utility of CVD risk models proposed in the 2016 Canadian
Cardiovascular Society Dyslipidemia Guidelines in identifying women
eligible for further assessment and treatment following hypertensive
disorders of pregnancy (HDP).
METHODS: All patients who deliver at Kingston General Hospital
and experience a HDP are considered for referral to the Maternal Health
Clinic for CVD risk assessment. The Preeclampsia New Emerging Team
(PE-NET) is a longitudinal prospective cohort study that recruited women
from Kingston General Hospital and Ottawa General Hospital who either
experienced preeclampsia or who had an uncomplicated pregnancy with

81A

no history of HDP. Using data collected from the Maternal Health Clinic
and the PE-NET, we evaluated the 2016 Canadian Cardiovascular Society
Dyslipidemia Guidelines' ability to identify CVD risk and need for further
treatment in women following pregnancy complicated by a HDP.
RESULTS: CVD risk for the HDP group significantly differed from
the PE-NET control group using the following risk scoring systems:
10-Year Modified Framingham Risk Score (FRS) (p<0.01), 30-Year
(p<0.0001), and Lifetime (p<0.0001). Using the 10-Year Modified FRS, all
participants were classified by the 2016 Canadian Cardiovascular Society
Dyslipidemia Guidelines as Low Risk, requiring no further follow-up.
Applying the 30-Year risk score resulted in a significant reclassification
of risk between the PE-NET Control and the HDP groups (p<0.001).
Similarly, the Lifetime risk score resulted in significantly different
risk classification between the PE-NET Control and the HDP groups
(p<0.0001), with 47.6% of HDP participants classified as High Risk, thus
warranting further follow-up.
Eligibility for Further Follow-Up Based on the 2016 Canadian Cardiovascular
Society Guidelines
Risk Score
10-Year Modified FRS
30-Year
Lifetime

Cohort

Eligible

Control (n=119)

HDP (n=320)

4 (1.3)

Control (n=119)

2 (1.7)

HDP (n=320)

39 (12.2)

Control (n=119)

17 (14.3)

HDP (n=319)

157 (49.2)

P-Value
NS
<0.001
<0.0001

CONCLUSION: The recommendations for risk classification using
the Modified FRS significantly underestimated lifelong CVD risk in the
HDP group compared to Control. Early primary prevention initiatives
among women with high 30-Year or high Lifetime CVD risk would
improve health outcomes, simultaneously preventing future burden on
the healthcare system.

O-074
Multiomics Analysis of the Immunome, Transcriptome, Microbiome,
Proteome, and Metabolome in Term Pregnancy. Sajjad Ghaemi†,
Martin Angst, Brice Gaudilliere, Nima Aghaeepour*, On behalf of the
March of DimesPrematurityCenterat Stanford University (47 coauthors).
Stanford University, Stanford, CA, United States.
INTRODUCTION: Recent technological advances in science provide
novel opportunities to unravel the complex biology of pregnancy.
Physiological changes during pregnancy are highly dynamic and
involve multiple interconnected biological systems. The simultaneous
interrogation of these systems with suitable technologies can reveal
otherwise unrecognized crosstalk. Understanding such crosstalk can
point to important disease mechanisms such as immune programming
by the microbiome, or specific interactions between proteins and cellular
elements, and ultimately guide new diagnostic and therapeutic strategies.
METHODS: We performed multiomics analysis of 51 samples from 17
pregnant women, delivering at term. Seven datasets were produced using
various high-throughput transcriptomic, immunological, microbiome, and
proteomic platforms. Dataset sizes ranged from tens to tens of thousands
of measurements, with different modularities and internal complexities.
A modified Elastic-net algorithm was used to measure the ability of each
dataset to predict gestational age. Using stacked generalization, these
datasets were combined into a single integrative model. These algorithms
were customized to account for the size and modularity of each unique
technology. Results were cross-validated on previously unseen patients.
RESULTS: The combined model produced a significantly higher
predictive power (Spearman R=0.95, p<1e-27) than that of any
individual biological assay. It also revealed novel interactions between
different biological modalities. A strong correlation was observed
between Gardnerella vaginalis and the frequency of B cells and TCRgd+
Tcells, a finding consistent with the unique role of TCRgd+ Tcells in
mucosal immunity. Other findings include a link between Chorionic
Somatomammotropin Hormone-1 (CSH-1) and the endogenous activity
of the transcription factor STAT5 measured at the single-cell level in

Friday Orals

Piezo1 Cation Channels: A Role in the Regulation of Uteroplacental
Blood Flow? Nga Ling Ko, Natalia Gokina, Liam John, George Osol*.
The University of Vermont, Burlington, VT, United States.
INTRODUCTION: Radial arteries, the primary site of vascular resistance,
are important in controlling uteroplacental blood flow (UPBF). During
gestation, the large increase in UPBF is facilitated by a combination of
vasodilation and expansive remodeling, and is mediated by nitric oxide
(NO). Piezo1, a novel cation channel, is reported to be a mechanosensor
for shear stress in different cell types, including endothelium, and has been
linked to eNOS activation. Here, we hypothesized that Piezo1 is present
in radial arteries, that its expression is augmented during pregnancy, and
that its activation leads to vasodilation via NO.
METHODS: 12-14 week old nonpregnant (n=6), mid-pregnant (day
15, n=5), and late-pregnant (LP: day 20, n=5) Sprague Dawley rats were
used for this study. Radial arteries were collected and processed for
immunofluorescence to determine Piezo1 cellular localization; protein
expression was compared by WB. Isolated, pressurized radial arteries
were used to evaluate the vasodilatory effects of Yoda1, a Piezo1 channel
activator, in the presence vs. absence of NOS inhibition (L-NNA+LNAME; 200 µM). Changes in cytosolic calcium in response to Yoda1
were measured following selective endothelial loading of arteries from
LP rats with fura-2.
RESULTS: Piezo1 was mainly localized in the radial artery endothelium,
but also present in medial smooth muscle. Its protein expression increased
with gestational age, with highest levels measured in vessels from LP rats.
In testing the functionality of Piezo1 during late pregnancy, Yoda1 (10 and
20 µM) induced vasodilation in a concentration-dependent manner (34±5
and 73±6 %). This response was associated with elevations in endothelial
calcium from 116±4 to 149±9 and 163±12 nM. Yoda1 vasodilation was
significantly reduced by NOS inhibition (40±7% @ 20 µM; p=0.005),
but only in LP vessels.
CONCLUSION: (1) Piezo1 channels are present in radial arteries and
are primarily localized to the endothelium. (2) Their expression increases
progressively during pregnancy, and (3) activation leads to increased
endothelial cell calcium and vasodilation which becomes increasingly
NO-dependent during gestation. This is the first demonstration that this
channel is both present and functional in uterine resistance arteries. Its
reported activation by shear stress and linkage to NO production suggest
that it may play an important role in gestational regulation of UPBF.

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