SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 114A

114A

Reproductive Sciences Vol. 25, Supplement 1, March 2018

Scientific Abstracts

T-011

T-013

Circulating Cathelicidin Antimicrobial Peptide LL-37 Levels in
Mothers and Preterm and Term Newborn Infants. Aurelija Dubicke†,
Eva Hell, Emma Fransson, Gunvor Ekman-Ordeberg, Kristina Gemzell
Danielsson, Giovanna Marchini. Karolinska Institutet, Stockholm, Sweden.
INTRODUCTION: Preterm infants are more susceptible to invasive
bacterial infection, which is a leading cause of morbidity and mortality in
this vulnerable population. The human cathelicidin peptide LL-37 is one of
the effector molecules of the innate immune system. It has antimicrobial
as well as immunomodulatory properties and plays an important role in
the first-line defense of newborn infants in the first weeks of life. Since
there are only few published data available, we aimed to further evaluate
the concentration of the peptide in maternal and cord serum samples from
different gestational age groups.
METHODS: Venous blood samples obtained from women during labor
delivered at preterm and term (n=28 before weeks 36 and n=15 between
weeks 37 and 42) and from the umbilical cord (n=28 born before week
36, n=27 born week 37-42) were analysed. The level of hCAP18/LL-37
was measured in serum by ELISA. The proform peptide hCAP18 and its
active form LL-37 were detected with western blot analysis.
RESULTS: There was a highly significant (p<0.001) correlation between
maternal and umbilical cord serum level of LL37 in both the pretem and
term group. There was no significant difference in serum levels of LL37
in preterm and term neonates or the respective groups of mothers. Both,
the proform hCAP18 and its active form LL37 were detected in the serum
of each group independent of gestational age.
CONCLUSION: We conclude that the similar level of hCAP18/LL-37
in preterm and term infants' serum may suggest a maternal passage of
the peptide in the early pregnancy. The increased vulnerability to central
nervous system infections does not seem to be related to the deficiency
in LL-37 peptide level in their serum.

Systematic Review of p38 MAPK in Reproductive Tissues. Samantha
Sheller-Miller†,4 Lauren Richardson†,4 Laura Martin†,1 Jin Jin†,2 Maria
Torloni,3 Ramkumar Menon*.4 1Botucatu Medical School, São Paulo State
University, Botucatu, São Paulo, Brazil; 2NanFang Hospital Southern
Medical University, Guangzhou, China; 3São Paulo Federal University,
São Paulo, Brazil; 4University of Texas Medical Branch, Galveston, TX,
United States.
INTRODUCTION: Oxidative stress (OS) plays a role in uterine tissue
remodeling during pregnancy and promoting parturition at term and
preterm. One of the responders to OS is p38 mitogen-activated protein
kinase (MAPK). Activated p38 MAPK (Phospho-p38) has been linked
to various functions in different gestational tissues during pregnancy and
parturition. However, a precise functional role for p38 MAPK is yet to
emerge. To fill this knowledge gap, a systematic review of literature was
conducted that described the functional role of p38 MAPK in various
intrauterine compartments (fetal membranes, placenta decidua, cervix,
and myometrium) during implantation, pregnancy, and parturition.
METHODS: We conducted a systematic review of literature on p38
MAPK expression and function reported in reproductive tissues during
pregnancy, published between 1980-2015 in English, using four electronic
databases (Web of Science, Pubmed, Medline, and CoCHRANE). The
selection of studies, data extraction and quality assessment was performed
in duplicate by two independent reviewers.
RESULTS: A total of 362 citations were identified, 85 were selected
for full-text evaluation and 78 were included for final review. Studies
were conducted predominantly using immortalized cells, primary cells
and tissue explants. Western blot was the most used approach to test p38
MAPK activation by phosphorylation, followed by immunolocalization.
p38 MAPK function is mostly studied in human placental trophoblast
cells (28%) followed by fetal membranes (24%), myometrium (23%),
decidua (19%) and remaining in the other cell/tissue types. p38 exists in
four isoforms and this specificity, as well as its expression and function
in the cervix, has never been reported. p38 activity is mostly reported in
association with inflammation or as a determinant of cell fate. Functional
activities of p38 are tissue and gestational age-dependent.
CONCLUSION: Based on studies published on p38 MAPK over the
last 35 years, various functional contributions of p38 MAPK have been
reported. For example, p38 is linked to cell differentiation, apoptosis, and
inflammation in human placental trophoblast cells and mostly studied as
an activator of COX-2 in myometrium. Current literature are insufficient
to provide a comprehensive description of p38 MAPK's role in gestation
and parturition in various uterine tissues. p38 MAPK's role in cervix is
yet to be studied. p38 MAPK is multifunctional, thus providing several
new avenues for research in reproductive and perinatal biology.

T-012
Replens Prevents Preterm Birth Thru a Non-Inflammatory
Mechanism. Christopher J Nold,1,2 Julie Stone,2 Kathleen O'Hara,2
Anthony Vella.2 1Hartford Hospital, Hartford, CT, United States;
2
University of Connecticut School of Medicine, Farmington, CT, United
States.
INTRODUCTION: The convergence of a multitude of factors promotes
inflammation in the reproductive tract as part of a final common pathway
leading to preterm birth. Replens, the vehicle used to deliver vaginal
progesterone, has not previously been studied in isolation as an agent to
prevent preterm birth. Therefore, these studies assessed if Replens will
have an effect on preterm birth using an inflammatory mouse model.
METHODS: For this study, pregnant CD-1 mice on embryonic day 17
(E17) received either: (1) An intrauterine injection of 250 ug of LPS; or
(2) An intrauterine injection of LPS on day E17 along with intravaginal
doses of 100 ul of Replens in the morning and evening on day E16 and
in the morning of day E17. Six hours after treatment with LPS, the
animals were evaluated for preterm birth and euthanized. The serum and
amniotic fluid were collected for multiplex analysis for TNF-α, IL-1β,
Rantes, and GM-CSF. The cervix was also collected for real time qPCR
for IL-6 and IFN-β.
RESULTS: Mice treated with LPS had a preterm birth rate of 87.5%
(started to deliver), while mice treated with LPS + Replens had a preterm
birth rate of 37.5% (p<0.005 chi square). The multiplex analysis of the
serum and amniotic fluid showed no difference in the concentration of
TNF-α, IL-1β, Rantes or GM-CSF between the mice treated with LPS or
those treated with LPS and Replens. Furthermore, there was no difference
in cervical expression of IL-6 and IFN-β between the two groups.
CONCLUSION: These studies demonstrate Replens prevents preterm
birth through a non-inflammatory mechanism. Further research is needed
to determine if Replens can be utilized as a therapeutic agent to prevent
preterm birth.
*Figure(s) will be available online.

T-014
Lactobacillus crispatus Protects Cervical Epithelial Barrier Function
in the Presence of a Pathogenic Bacteria, Gardnerella vaginalis.
Lauren Anton, Ann DeVine, Amy G Brown, Luz-Jeannette Sierra, Laura
Heiser, Michal A Elovitz*. University of Pennsylvania, Philadelphia,
PA, United States.
INTRODUCTION: Spontaneous preterm birth (PTB) is hypothesized
to be associated with premature cervical remodeling initiated by cervical
epithelial barrier breakdown. Microbial communities in the cervicovaginal
(CV) space are likely to contribute to the integrity of the cervical epithelial
barrier. Colonization with Lactobacillus crispatus (L. crisp) is thought
to represent CV health. While colonization by Gardnerella vaginalis (G.
vag) is associated with the diagnosis of bacterial vaginosis and is thus
considered an unhealthy CV state. We sought to investigate the biological
effects of G. vag and L. crisp on cervical epithelial function and whether L.
crisp has the ability to mitigate the potential pathogenic effects of G. vag.
METHODS: Human ectocervical cells (Ect1/E6E7) (Ecto) were
treated with a total of 10% v/v sterile filtered L. crisp or G. vag cell free
supernatants (CFS) alone or in combination (n=6-9). Ecto cells were
exposed to L. crisp CSF on day 1 followed by G. vag CSF on day 2 or
vice versa for 24-48hrs. The following treatment groups were studied 1)
control, 2) L. crisp, 3) G. vag, 4) L. crisp+ G. vag and 5) G. vag+ L. crisp.
Table of Contents for the Digital Edition of SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018
