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Reproductive Sciences Vol. 25, Supplement 1, March 2018

METHODS: Images collected at delivery of MC twins with arterial and
venous circulations injected with colored paints were traced to identify
the networks. Anastomoses were marked as the mid position of a shared
vessels measured from the last branch point. Distances of anastomoses
to nearest vessel branch points were measured and identified as either
branch points of arteries or of veins. 30 cases of MC twins with birth
weight discordance (BWD) <20%, and 15 cases each of MC twins with
BWD >20%, or the twin anemia-polycythemia syndrome (TAPS) were
analyzed. Distances between points were normalized to placental size.
Nonparametric tests and principal components analysis (PCA) were used
to compare the three groups.
RESULTS: The greater the number of AA anastomoses, the farther
were the nearest vessels in MC twins without BWD and in TAPS, but no
relationships were found in MC with BWD>20%. The greater the number
of VV anastomoses, the farther the vessels in MC with and without BWD,
but there was no relationships in TAPS. The number of AV anastomoses
did not impact local vessel proximity. PCA was performed in the MC
without BWD and the factors weights were applied to the other groups.
Factors identified in MC without BWD were strongly correlated with
gestational and summed BWs. The same factors were also strongly
correlated in MC with BWD, but none of the vascular relationships defined
in the MC without BWD had any predictive value in TAPS.
CONCLUSION: Our prediction that AA and VV anastomoses that might
be expected to alter local pressures and directions of flow would impact
local surface vascular features while AV anastomoses might not disturb
local vasculature is supported by our findings. PCA identifies patterns
of related measures; each "factor" indicates a group of such variables.
While TAPS has some similarity with MC without BWD in regards to
impacts of AA anastomoses, PCA suggests TAPS networks are overall
unique structures that, in this analysis, have few global similarities with
MC twins with or without BWD.

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Progesterone Suppressed Ex Vivo Pregnancy Immune Responses Are
Reversed with the Progesterone Antagonist RU486. Nishel M Shah†,
Gavin Sooranna†, Nesrina Imami, Mark R Johnson. Imperial College
London, London, United Kingdom.
INTRODUCTION: Progesterone (P4) is an important hormone for the
establishment and maintenance of pregnancy and its functional withdrawal
in reproductive tissue is associated with the onset of parturition. However,
the effects of P4 on the adaptive immune response is poorly understood. By
taking a novel approach and comparing the effects of P4 supplementation
and the use of a P4 antagonist mifepristone (RU486) ex vivo in pregnancy,
we were able to demonstrate the immune-modulatory functions of P4.
METHODS: For the control group, healthy pregnant patients (n=42)
were recruited during their first visit before 20 weeks of gestation. Once
recruited, these patients were asked to provide peripheral blood samples
longitudinally. The time points for sample collection were: at recruitment
(range 11-20 weeks of gestation), 28 weeks, 34 weeks, in labor or at
delivery, 24 hours postnatal, and 6-8 weeks postnatal. The control group
were compared to pregnant patients receiving P4 supplementation
(n=15). In addition, pregnant patients (n=8) undergoing medically
indicated terminations of pregnancy due to fetal anomaly in an otherwise
uncomplicated pregnancy were recruited from the fetal medicine unit to
study the effects of P4 antagonism using RU486. In each patient group,
a combination of sensitive ELISpot assay, multiplex and flow cytometry
was undertaken.
RESULTS: We demonstrate that in pregnancy the immune system is
increasingly activated (CD38, CCR6) with heightened antigen-specific
cytotoxic T cell responses (granzyme B). Simultaneously, pregnancy
promotes a tolerant immune environment (IL-10 and regulatory-T cells)
that gradually reverses prior to the onset of labor. P4 suppresses and
RU486 enhances antigen specific CD4 and CD8 T cell inflammatory
cytokine (IFN-γ) and cytotoxic molecule release (granzyme B). P4 and
RU486 effectively modulate immune cell-mediated interactions, by
regulating differentiated memory T cell subset sensitivity to antigen
stimulation.

Scientific Abstracts

CONCLUSION: Our results indicate that P4 and RU486, as immune
modulators, share a reciprocal relationship. This data unveils key
contributions of progesterone and RU486 on the maternal immune
system and paves the way for future clinical work on the use of these in
immunotherapy.

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Labour is Associated with a Decline in Treg Function and Their
Modulation of TLR-Ligand Induced Immune Responses. Nishel M
Shah†, Lydia Edey†, Gavin Sooranna†, Orene Greer†, Nesrina Imami,
Mark R Johnson*. Imperial College London, London, United Kingdom.
INTRODUCTION: Sepsis in pregnancy remains an important cause
of maternal death. The incidence of severe maternal sepsis is increasing
and patients with complex medical problems being at greatest risk. The
immunomodulatory effect of pregnancy, designed to prevent immune
mediated rejection of the fetus, has been suggested to make a pregnant
woman more susceptible to sepsis, but there is little evidence to support
this. Prospective studies have suggested that labour and the puerperium
carry a 2-3-fold increase in the risk of sepsis compared to the antenatal
period.
METHODS: We investigated whether labour was associated with changes
in the adaptive and/or innate immune system, by studying the changes
in cell number, activation status and functional behaviour of peripheral
blood, myometrial and cord blood mononuclear cells at the onset of labour.
Our aim was to test the hypothesis that human labour is associated with
a decline in Treg function, specifically their modulation of TLR-ligand
induced immune responses.
RESULTS: We show that labour is associated with increased immune
responsiveness at the maternal-fetal interface with greater expression of
MHC class II molecules on CD4 T cells, and diminished Treg repression
to infective and inflammatory stimuli. This is in part due to a change
in Treg phenotype. In contrast, the innate arm of the immune system
during parturition is perfectly poised to respond to microbial stimuli
and inflammation, as shown by with altered monocyte, NK and iNKT
phenotype. This combination of features may influence the observed
increased proportions of inflammatory CBMC from neonates born to
labouring mothers.
CONCLUSION: Collectively, our results show that labour is unique
in that it is accompanied by a protective loss of Treg mediated immune
tolerance and T cell responses to inflammation, which is unlike the typical
response in sepsis where an expanded population of Tregs serve to aid
recovery in severe illness. Additionally, labour is characterised by an
enhanced innate response to inflammatory and infective stimuli, and a
shift towards TH1 responses in cord blood. Our results help to explain the
contribution of modulated adaptive immune responses during labour that
leave mothers at a greater risk of complications associated with sepsis.

S-191
Allopurinol Inhibits Excess Glucose-Induced Trophoblast
Inflammatory and Angiogenic Responses. Masaru Negi†,2 Melissa J
Mulla,2 Christina S Han,1 Vikki M Abrahams*.2 1UCLA, Los Angeles, CA,
United States; 2Yale University, New Haven, CT, United States.
INTRODUCTION: Pre-gestational diabetes is a significant risk factor
for development of pregnancy complications associated with placental
dysfunction, such as preeclampsia. In past studies, we reported that
hyperglycemic levels of glucose-induced a pro-inflammatory and
dysregulated angiogenic profile in trophoblast cells by elevating the
secretion of IL-1β; IL-8; sFlt-1; sEndoglin; and PlGF. The IL-1β response
to excess glucose was mediated by the upregulation of uric acid, which in
turn activated the NLRP3 inflammasome. Allopurinol is a xanthine oxidase
inhibitor that is used medically, including in pregnancy, and prevents
NLRP3 inflammasome activation by inhibiting uric acid and reactive
oxygen species (ROS) production. Studies in the placenta have focused
on the ability of allopurinol to reduce oxidative stress, but its ability to
reduce inflammation in pregnancy is not known. The aim of this study was
to test the effects of allopurinol on excess glucose-induced trophoblast
inflammation and angiogenic factor production in vitro.



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

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SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - Cover3
SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - Cover4
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2020
https://www.nxtbook.com/nxtbooks/sage/psychologicalscience_demo
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2020
https://www.nxtbook.com/nxtbooks/sage/fai_202009
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_august2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2020
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2019
https://www.nxtbook.com/nxtbooks/sage/fai_201909
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_july2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2019
https://www.nxtbook.com/nxtbooks/sage/canadianpharmacistsjournal_05062019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2019
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201903
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2019
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2018
https://www.nxtbook.com/nxtbooks/sage/tec_20180810
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2018
https://www.nxtbook.com/nxtbooks/sage/fai_201807
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_april2018
https://www.nxtbook.com/nxtbooks/sage/sri_supplement_201803
https://www.nxtbook.com/nxtbooks/sage/slas_discovery_201712
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_february2018
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_december2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_november2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_october2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_september2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_julyaugust2017
https://www.nxtbook.com/nxtbooks/sage/fai_supplement_201709
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_june2017
https://www.nxtbook.com/nxtbooks/sage/hospitalpharmacy_may2017
https://www.nxtbook.com/nxtbooks/sage/fai_201706
https://www.nxtbook.com/nxtbooks/sage/fai_201607
https://www.nxtbookmedia.com