SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 113A

Scientific Abstracts

T-008
Fetal Membrane Organ on Chip: An Innovative Approach to Study
Feto-Maternal Cellular Interactions. Lauren Richardson†,1 Tianbing
Ding,2 Juan Gnecco,2 Kevin Osteen,2 David Aronoff,2 Ramkumar Menon.1
1
UTMB, Galveston, TX, United States; 2Vanderbilt University Medical
Center, Nashville, TN, United States.
INTRODUCTION: The fetal membrane, a vital component that helps
to maintain pregnancy and contribute to parturition signaling, is often
studied in segments due to its structural complexity and composition of
both fetal and maternal layers. Transwell systems are traditionally used
to study different cell interactions; however, the usefulness of these static
systems is limited. To overcome these difficulties fetal-maternal cell
organ-on-chip (OOC) models are devised to better understand in vivo-like
cellular interactions. This study compared interactive properties of amnion
epithelial cells (AECs) and decidual cells cultured in a two chamber OOC
device and traditional transwell.
METHODS: De-identified tissue samples were provided by the
Cooperative Human Tissue Network, which is funded by the National
Cancer Institute. Primary AECs and decidual cells from term fetal
membranes were used for this study. A two chamber (top and bottom)
OOC device made of silicone elastomer and sandwiched between a
polycarbonate membrane was developed. AECs and decidual cells were
plated in the top bottom chamber of OOCs respectively. FITC based
membrane permeability assay was carried out for 1 and 2 hours. Cells
were treated with oxidative stress (OS) inducer, cigarette smoke extract
(CSE; 1:50), one chamber at a time for 48 hours to test interactive changes.
Similarly, transwell cultures of same cell preparations and treatment were
used for comparisons.
RESULTS: Compared to trans-well cultures, the two cell OOC model
produced better membrane permeability regardless of side of treatment
or time point. Membrane permeabilization was higher in AECs treated
with CSE compared to similar treatment on decidual side. In OOC, CSE
treatment produced better interaction between cellular layers. This was
evident when OS induced senescence on one side of the chamber produced
similar changes on the opposite side suggesting transfer of biochemicals
between layers that can induce changes. In contrast, this effect was
minimal in transwell system.
CONCLUSION: The controlled environment of an OOC allows improved
signal propagation between cells by minimizing noise highlighting the
small changes between treatments that cannot be seen in conventional
transwell devices. Fetal membrane OOC model provides better interaction
between cell types that can be used to study feto-maternal signaling during
pregnancy than currently employed transwell systems.

T-009
Nonlinear Logistic Regression Analysis of Electrical Impedance
Spectroscopy Data Improves the Accuracy of Prediction of Preterm
Birth. S Zhang†, Y Zhu†, L Zhao†, Zi-Qiang Lang, Victoria Stern†,
Timothy J Healey, Brian Brown, Andrew Humphries, Dilly O Anumba*.
University of Sheffield, Sheffield, United Kingdom.
INTRODUCTION: Assessing the risk of preterm birth (PTB) in
mid-trimester remains problematic because current clinical methods
(ultrasound cervical length and cervicovaginal fibronectin quantitation)
have high false positive rates. We have recently shown that cervical
electrical impedance spectroscopy (EIS) may be an alternative method
for predicting PTB. However, conventional EIS analysis involves linear
logistic regression models using only the magnitude of impedivity of the
EIS data, an approach which does not consider the complex relationship
that may exist between tissue resistivity changes associated with cervical
remodelling and PTB. We hypothesized that a more advanced nonlinear
logistic regression analysis that incorporates both phase and magnitude
EIS data may improve the predictive accuracy of cervical EIS for PTB.

113A

Objectives: We aimed to compare the predictive performance of linear
and advanced nonlinear logistic regression analysis for cervical EIS-based
prediction of PTB in asymptomatic women in mid-trimester. For the first
time, both the magnitude and phase data derived from cervical EIS were
included in prediction models.
METHODS: Data from 117 high-risk pregnant women who underwent
cervical EIS at 20-22 weeks (V1) and 26-28 weeks (V2) were compared
for predictive accuracy for delivery before 37 weeks gestation using linear
logistic and more advanced nonlinear logistic regression analysis. Firstly, a
random training data set of 77 patients (16 preterm and 61 term deliveries)
was used to develop linear and nonlinear logistic regression models. These
models were then applied to a testing set of 40 patients (10 preterm and 30
term deliveries) to determine predictive accuracy for delivery before 37
weeks, expressed as the areas under the Receiver Operator Characteristic
(AUC) curve plots of sensitivity against specificity.
RESULTS: Of the 117 asymptomatic women studied at 20-22 (V1) weeks
and 26-28 weeks (V2), prediction of PTB improved from AUC 74%,
sensitivity 80%, and specificity 67% with the linear analysis to AUC 82%,
sensitivity 80%, and specificity 80% with the more advanced nonlinear
analysis, suggesting that, compared to linear analysis, the non-linear
logistic regression model provided better predictive accuracies for PTB
and showed more reliability and consistency across randomly generated
training and testing sets.
CONCLUSION: Non-linear logistic regression based multivariate
analytical tools may enhance predictive accuracies of cervical EIS for
PTB and warrants further study.

T-010
Decorin and Biglycan Are Required for Cervical Extracellular
Matrix Structure in Pregnancy. Shanmugasundaram Nallasamy†,2
Nicole Lee†,1 Charles Jayyosi†,1 Kristin Myers,1 Mala Mahendroo*.2
1
Columbia University, New York, NY, United States; 2UT Southwestern
Medical Center, Dallas, TX, United States.
INTRODUCTION: Small leucine rich proteoglycans (SLRPs) are
established factors that regulate collagen fibrillogenesis and their deletion
results in impaired connective tissue function and strength. We recently
reported that mice deficient in decorin, a prototype member of the SLRP
family, have disrupted collagen and elastic fiber structure and tissue
mechanical function in the nonpregnant and early pregnant mouse cervix
with transient recovery during late pregnancy. While mice with a targeted
mutation in decorin or the related SLRP biglycan do not have a parturition
defect, deletion of both decorin and biglycan results in parturition defects
indicating a compensatory role of these SLRPs. Ongoing studies are
focused on understanding the role of decorin and biglycan in extracellular
matrix (ECM) structure and function during cervical remodeling.
METHODS: Decorin and biglycan null mice were assessed. The
ultrastructure of collagen was analyzed through transmission electron
microscopy (TEM). Mechanical testing was conducted to assess the
biomechanical properties of the tissue.
RESULTS: In preliminary studies, we have determined that loss of
biglycan alone does not cause defects in collagen fibril ultrastructure in
the nonpregnant and early pregnant mouse cervix as was observed in the
decorin null mouse. Interestingly, deletion of both decorin and biglycan
results in severe abnormalities of collagen fibril ultrastructure, spacing,
and abundance in the nonpregnant cervix as well as throughout pregnancy.
CONCLUSION: Decorin and biglycan play a significant role in
regulating cervical ECM structure and biomechanical function.
Specifically, this study demonstrates that decorin can fully compensate
for the loss of biglycan while biglycan can only partially compensate
for the loss of decorin in guiding collagen fibrillogenesis. Further, it is
inferred that decorin is the predominant SLRP required for cervical ECM
function. Ongoing experiments will address the molecular mechanisms
by which decorin and biglycan regulate collagen fibrillogenesis in the
mouse cervix. Overall, these studies will advance our understanding of
the cervical remodeling process, which may potentially help to manage
clinical conditions associated with cervical dysfunction such as cervical
insufficiency and preterm birth.

Thursday Posters

appears to plays a key role during the onset of spontaneous parturition;
these studies have provided additional support for the hypothesis that
cfDNA released by the placenta and fetal membranes is able to trigger
such proinflammatory events. (Funded by the Burroughs Welcome FundPreterm Birth Initiative)

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