SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 255A

Scientific Abstracts

CONCLUSION: These data demonstrate pregnancy related
preconditioning-like events allow for non-apoptotic tocolytic CASP3
action. We speculate that inappropriate preconditioning may predispose
women to an increased risk of preterm birth through precocious
prostaglandin production triggered by the onset of apoptotic caspase-3 in
the uterine compartment. 1Kyathanahalli et al., PNAS, 2015

S-003

S-004
Beneficial Effects of Enriched Environment on the Prevention of
Lipopolysaccharide Induced Preterm Labor. Ana Franchi*. CEFYBO,
Buenos Aires, Argentina.
INTRODUCTION: Preterm birth (PTB), defined as childbirth occurring
before the week 37 of gestation, is a major determinant of neonatal
mortality and morbidity. Prenatal infection and consequent inflammation
are the main causes of PTB and in turn, are key risk factors for the
later development of cerebral palsy and neonatal sepsis. Our group
developed a murine model of PTB, induced by injections of bacterial
lipopolysaccharide (LPS) that produces an 85% of PTB. The effects of
environmental enrichment (EE), which are mainly positive, are manifested
by different molecular, cellular and physiological changes. And in
general EE appears to be associated with an overall improvement in the

255A

psychological and physical wellbeing of animals. The aim of this work
was to evaluate the effect of exposition to an EE as a potential treatment
for reducing PTB rate in our mouse model.
METHODS: The EE protocol consisted in housing a group of ten six
week old BALB/c females in larger cages containing a variety of objects,
stairs, walkways, tunnels and wheels that provide optimal conditions for
further exploration, visual, cognitive, social interaction and voluntary
exercise activity. Standard conditions (control environment, CE) consisted
of standard laboratory cages that housed 4 animals. After 6 weeks females
were mated with males in regular cages and then pregnant females returned
to EE (or CE) cages till day 15th of pregnancy, when LPS (or saline
solution) was administered to evaluate percentage of PTB.
RESULTS: So far we observed that pretreatment with EE felt by
35% LPS-induced PTB and offspring born from these mothers had a
normal development. To evaluate possible mechanisms involved in this
phenomenon we have studied different inflammatory mediators in uterus,
and observed an impact of EE in the expression levels of CD14 and TLR-4
that were significantly diminished (p<0.05). Similarly, we observed that
EE treatment significantly prevented the increase of uterine NOS and
cervical MMP9 activity and plasma corticosterone levels induced by LPS
(p<0.05). Moreover, we analyzed leucocyte infiltration in cervix and uterus
and observed that LPS increased leucocyte infiltration in both groups but
we found epithelial infiltration only in CE treated mice.
CONCLUSION: Collectively, our results showed a protective effect of
the enrichment of the environment against an immune challenge during
pregnancy.

S-005
The Effects of Fetal Station on NTSV Labor: Not What We Were
Taught. Megan C Oakes†,2 Erica Wu,2 Melissa Westermann†,2 Brian A
Crosland†,2 Emily Seet*,1 Kiran Clair†,2 Kenneth Chan*.1 1Miller Women
and Children's Hospital/Long Beach Memorial Medical Center, Long
Beach, CA, United States; 2University of California, Irvine, Orange,
CA, United States.
INTRODUCTION: To investigate fetal station as a predictive variable
for vaginal delivery in nulliparous, term, singleton, vertex (NTSV) patients
with NICHD-defined active-phase arrest in the first stage of labor.
METHODS: This is a retrospective chart review of 466 NTSV patients
delivered between January 2013 and May 2017 at an academic community
hospital, where resident physicians manage labor under supervision of
an on-site attending. We identified women with protracted active labor:
≥ 6 cm without cervical change for at least a 4-hour period and evaluated
whether starting fetal station or change in station during the protracted
period influenced the prospect of vaginal delivery.
RESULTS: We identified 98 women with protracted active labor. For
those with protracted labor 4-6 hours (n=49), there was no difference in
vaginal delivery rate whether the fetus was engaged (<0 station [n=25]) or
unengaged (≥ 0 station [n=24]) at the start of the protracted period, 80.0 vs.
83.3%, p=0.8 (Table 1). However, in those with protracted labor > 6 hours
(n=49), engaged fetal station (n=16) at the start of protraction portended
a lower vaginal delivery rate compared to those unengaged (n=33), 18.8
vs 54.6%, p=.02 (Table 1). A change in fetal station (without change in
dilation) did not increase vaginal delivery rates whether a patient had a
protracted labor from 4-6 hours (n=49) or > 6 hours (n=49) (Table 2).
This study is powered to assess the effect of starting station and change
in station on vaginal delivery rates in those protracted 4-6 hours and in
the comparison of those protracted > 6 hours.
CONCLUSION: Contrary to past dogma, we found that change in station
did not predict improved vaginal delivery rates while in a protracted,
active-phase labor. In fact, we found those with starting station >0 were
less likely to deliver vaginally when protracted active labor lasted > 6
hours. The study is limited by the nature of standardizing fetal station
assessment; however, it is useful in identifying cervical dilation as the
key variable for change in the active phase.

Saturday Posters

Inhibition of Sphingosine Kinase Attenuates the Pro-Inflammatory
Response in In-Vivo and In-Vitro Models of Inflammation Induced
Preterm Birth. Kiersten Giusto†,2 Sandra E Reznik*.1,2 1Montefiore
Medical Center/Albert Einstein College of Medicine, Bronx, NY, United
States; 2St. John's University, Queens, NY, United States.
INTRODUCTION: Preterm birth (PTB) affects an estimated 15 million
babies born every year and occurs in 9.6% of births in the United States.
The most common cause of spontaneous preterm birth is inflammation.
Evidence has demonstrated the role of endothelin-1 (ET-1) as a constrictor
of myometrial smooth muscle and as a pro-inflammatory mediator.
Sphingosine kinase (SphK) acts downstream of ET-1 and can activate other
pro-inflammatory mediators leading to myometrial contraction. SphK
phosphorylates sphingosine to sphingosine-1-phosphate (S1P), which is
an intracellular and extracellular messenger that affects calcium release
and an inflammatory mediator of transcription. Recently, we showed
that SphK inhibition prevents lipopolysaccharide or recombinant tumor
necrosis factor alpha (rTNFα) induced birth in a murine model. We now
show that varying concentrations of SKI II significantly decrease the
concentration of inflammatory cytokines released from human placental
trophoblast cells (HTR-8/SVneo) after stimulation with recombinant
human TNFα (hTNFα).
METHODS: The human placental trophoblast cell line HTR-8/SVneo
was used to study the profile of pro-inflammatory cytokines release
after stimulation with hTNFα. The cells were pretreated with varying
concentrations of SKI II (0.1, 1, and 10 μM). Two hours after treatment,
cells were stimulated with 20ng/ml recombinant hTNFα for 24 h. The cell
supernatant was collected at T= 24 h and the pro-inflammatory cytokine
profile was determined using ELISA.
RESULTS: Previously, we reported that inhibition of SphK with SKI II
significantly decreased the percent of rTNFα-challenged timed pregnant
mice delivering prematurely from 88.9% to 25.0%, (p < 0.05). None of
the pups tracked in our previous study showed evidence of teratogenic
effects and no toxic effects were observed in the dams. To test whether
these results have relevance in a human system, we examined the profile
of pro-inflammatory cytokines in HTR-8/SVneo cells after stimulation of
the cells with hTNFα and treatment with varying concentrations of SKI
II. Treatment of 100 μM SKI II significantly decreased the levels of IL-6
(P<0.01) and MCP-1 (P <0.0001) and showed a trend towards a decrease
in IL-8 secretion in the collected supernatant.
CONCLUSION: Inhibition of sphingosine kinase may have applications
in the management of inflammation induced preterm birth as evidenced
through its effect on PTB in the in vivo model of PTB and its ability
to decrease cytokine release in a human placental trophoblast cell line.

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
