SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 282A

282A

Reproductive Sciences Vol. 25, Supplement 1, March 2018

0.57 ± 0.028 vs MO, 0.30 ± 0.041 µmol cytochrome c/min), complex IV
(C, 7666 ± 941 vs MO, 5164± 528 mmol cytochrome c/min) (p<0.05). The
decreased activities were more evident in the L lobe except for complex
I where the R lobe was more affected. Regarding antioxidant systems,
GSH decreased in the MO fetal L lobe (p=0.0260). Gl-Px activity, lipid
peroxidation MDA, and vitamin E showed no alteration.
CONCLUSION: Although hepatic mtDNA copy number was
increased in MO fetal livers, all respiratory chain complex activities
measured were decreased in the same group, being more evident in
the L lobe. MO also decreased antioxidant capacity in the L lobe,
possibly predisposing to altered mitochondrial function and redox
homeostasis later in life. Funding: FEDER/COMPETE/FCT-Portugal
(PTDC/DTP-DES/1082/2014, POCI-01-0145-FEDER-007440, OCI01-0145-FEDER-016657, SFRH/BPD/116061/2016 t and SFRH/
BPD/101169/2014), and NIH (R01HD070096-01A1).

S-090
A Pilot Study of Circulating miRNAs as Potential Biomarkers for
Small-for-Gestational-Age Births. Sung Hye Kim†,1 Reem Binkhamis†,1
Joanna R Cook†,1 David A MacIntyre,1 Lynne Sykes,1 Shirin Khanjani,1
Phillip R Bennett,1 Vasso Terzidou.1,2 1Imperial College London, London,
United Kingdom; 2Imperial College School of Medicine, Chelsea and
Westminster Hospital, London, United Kingdom.
INTRODUCTION: Small-for-gestational-age (SGA) babies are neonates
whose birth weight is less than the 10th centile for that particular gestational
age. SGA is associated with increased risk of stillbirth and long term
adverse outcomes such as cerebral palsy. Current screening practices
of high-risk patients fail to detect approximately three quarters of SGA
babies before birth and an even higher proportion (~85%) are missed
in low-risk pregnancies. Therefore, early identification of SGA babies
is essential for improved antenatal care. In this study we investigated
the ability of circulating plasma miRNAs to determine the risk of SGA
among pregnant women.
METHODS: The study included serial maternal plasma samples collected
throughout the second trimester (12-22 weeks) from 29 pregnant women
where 16 had normal growth at term and 13 had growth restricted babies
(birth weight of <5th centile). A total of 800 miRNAs were profiled using
the nCounter miRNA profiling assay. Multivariate partial least-squares
discriminant analysis (PLS-DA) was performed using SIMCA-P and a list
of differential miRNAs was identified based on a variable importance of
projection (VIP) score of >1 in the PLS-DA. Potential miRNAs and ratios
of selected miRNAs predictive for SGA were analysed using univariate
statistics in GraphPad Prism. The top 8 candidate miRNA biomarkers
identified were validated by RT-qPCR.
RESULTS: Eight miRNAs (hsa-miR-374a-5p, hsa-let-7d-5p, hsamiR-4454, hsa-miR-7975, hsa-miR-191, hsa-miR-107, hsa-miR-146a5p, hsa-miR-30e-5p) were found to be differentially expressed (p<0.01)
in SGA cases. These were technically validated in samples at 12-14+6
weeks using RT-qPCR. From the top 8 candidate miRNA biomarkers,
hsa-miR-374a-5p, hsa-let-7d-5p, hsa-miR-4454, and hsa-miR-7975
showed the strongest ability to differentiate SGA from normal weight
births (AUC>0.85).
CONCLUSION: The circulating plasma miRNAs identified in this
study are potential candidate biomarkers for the early prediction of SGA
births. Further independent biological validation studies are required to
investigate the clinical applications of these biomarkers.

Scientific Abstracts

S-091
Effect of Nifedipine on Fetal Central Hemodynamics and Cardiac
Function during Hypoxemia in a Chronic Sheep Model. Leena Alanne,3
Amarnath Bhide,6 Juulia Junno,4 Heikki Huhta,4 Merja Kokki,3 Mervi
Haapsamo,5 Ganesh Acharya*,2 Juha Räsänen*.1 1Helsinki University
Hospital, Helsinki, Finland; 2Karolinska Institute, Stocholm, Sweden;
3
Kuopio University Hospital, Kuopio, Finland; 4Oulu University Hospital,
Oulu, Finland; 5Satakunta Central Hospital, Pori, Finland; 6St George's
Hospital, London, United Kingdom.
INTRODUCTION: Nifedipine is commonly used in pregnancies
complicated by placental insufficiency. Fetal hypoxemia is often found
in placental insufficiency. We investigated whether nifedipine has any
detrimental effects on fetal central hemodynamics and cardiac function
during hypoxemia. We hypothesized that fetal cardiac function and central
hemodynamic responses to hypoxemia are not altered by nifedipine.
METHODS: A total of 21 pregnant sheep underwent surgery
approximately 127 days of gestation (term 145 days) for fetal
instrumentation. After a 5-day recovery period, experiments were
performed under general anesthesia. Fetal carotid artery blood pressure
and blood gas values were monitored. Ductus arteriosus volume blood
flow (Qda) was measured by ultrasonic transit-time flow probe. By pulsed
Doppler ultrasonography, fetal left (LVCO) and right (RVCO) ventricular
cardiac outputs and right pulmonary artery pulsatility index (RPA PI)
values were obtained, and ventricular function was examined using tissue
Doppler echocardiography. After baseline data collection, maternal and
fetal hypoxemia were induced. Hypoxemia phase data were collected
after 30 minutes' hypoxemia. Thereafter, in 9 fetuses nifedipine infusion
was started and 12 fetuses served as controls receiving saline infusion.
Data were collected 30 and 120 minutes after infusion was started.
Then maternal oxygenation was returned to baseline, while infusion
was continued, and recovery phase data were collected 30 minutes after
achieving maternal normoxemia.
RESULTS: Hypoxemia decreased significantly fetal pO2, pH, base excess
and increased lactate values in both groups. In the recovery phase, fetal
pO2 did not return to the baseline in nifedipine group. Nifedipine did not
affect fetal mean arterial pressure. During hypoxemia fetal Qda increased
significantly in both groups, while cardiac outputs remained stable in both
groups during the experiment. In both groups, RPA PI values increased
during hypoxemia, in nifedipine group significantly. Tissue-Doppler
derived LV isovolumic contraction and relaxation velocities and RV
isovolumic relaxation velocity and its deceleration decreased significantly
only in the nifedipine group during hypoxemia.
CONCLUSION: Nifedipine does not alter fetal central hemodynamic
responses to hypoxemia. However, in hypoxemic fetus, nifedipine
decreased LV contractility, and both LV and RV relaxation. Nifedipine
can have detrimental effects on fetal cardiac function in hypoxemia.

S-092
AMPK Activation in High Altitude-Exposed Pregnant Mice is
Reduced in Uterine Artery and Increased in Placenta. Sydney L
Coates†, Alexandrea S Doyle†, Elise S Bales, Ramon A Lorca, Colleen
G Julian, Lorna G Moore*. University of Colorado, Aurora, CO, United
States.
INTRODUCTION: The chronic hypoxia of high altitude (HA, >2500 m)
raises the frequency of preeclampsia and intrauterine growth restriction
threefold due, in part, to a reduction in the pregnancy-associated rise
in uterine artery (UtA) blood flow. Vascular adenosine monophosphate
kinase (AMPK) activation is important in regulating systemic blood
flow, and is dysregulated in vascular disease. Our studies suggest that
AMPK activation plays a role in defending human uteroplacental blood
flow and fetal growth under conditions of chronic hypoxia, and induces
vasodilation in isolated murine UtA. Here, we sought to localize AMPK
in murine UtA and to determine the influence of HA exposure on UtA
and placental AMPK localization and activation.
METHODS: The main UtA and placentas were collected from E18.5
C57BL/6 mice gestated from E14.5-18.5 at simulated sea level (SL, n=3)
or HA (18,000 ft., n=7) using hyperbaric or hypobaric chambers. UtAs
were paraffin-embedded and immunofluorescent stained using antibodies

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