SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 70A

70A

Reproductive Sciences Vol. 25, Supplement 1, March 2018

and a significant decrease in ADM protein expression(p= 0.008). Thus,
the reduced circulating levels of ADM mRNA may have placental origins.
The maternal endothelium is another potential site that may mediate
the reduction in ADM. When we added either trophoblast conditioned
media or TNFα to endothelial cells (HUVECs), we confirmed that both
significantly reduce ADM mRNA expression (p<0.0001). Endothelial
dysfunction in our model was evidenced by an increase in VCAM1 in
response to the addition of both trophoblast conditioned media and TNFα.
CONCLUSION: Circulating ADM mRNA levels are significantly
decreased among women with preterm PE, and among asymptomatic
women at 28 or 36 weeks destined to develop PE. Our functional
studies suggest that the alterations in ADM mRNA expression may be
of placental and/or endothelial cell origin. Our findings suggest ADM
mRNA has potential as a biomarker for PE, alone or in combination
with other circulating molecules and warrants validation in further
prospective studies.

O-040
Regulatory T Cells Regulate Uterine Artery Function to Impact Fetal
Growth. Alison S Care†,1,2,3,4 Stephane L Bourque*,3,4 Jude S Morton*,3,4
Emma P Hjartarson†,3,4 Sarah A Robertson*,1,2 Sandra T Davidge*.3,4
1
Robinson Research Institute, Adelaide, Australia; 2University of Adelaide,
Adelaide, Australia; 3University of Alberta, Edmonton, AB, Canada;
4
Women and Children's Health Research Institute, Edmonton, AB, Canada.
INTRODUCTION: Preeclampsia and fetal growth restriction remain
important causes of maternal and perinatal morbidity and mortality. In
these conditions, a deficiency in regulatory T (Treg) cells, a specialized
subset of lymphocytes, has been observed. Treg cells prevent maternal
immune rejection of the fetus, but also contribute to vascular homeostasis
in non-pregnant rats. We hypothesize that a reduced Treg cell population
would cause inflammation and uterine artery dysfunction during
pregnancy.
METHODS: FOXP3 is a master transcription regulator in Treg cells.
Transgenic Foxp3-DTR mice have FOXP3 promoter-driven expression of
the human diphtheria toxin (DT) receptor to enable selectively depletion
of FOXP3+ (Treg) cells. DT was injected (37.5ng/g) on gestational day
(GD)3.5 and GD5.5 to selectively deplete FOXP3+ cells; PBS-treated
Foxp3-DTR mice served as controls. On GD9, ultrasound biomicroscopy
was performed to assess uterine hemodynamics. On GD10.5 mice were
either anesthetized and systemic hemodynamics were assessed using
indwelling catheters in the carotid artery, or euthanized and tissues
harvested for the study of isolated vascular function using wire myograpy.
In a separate group, fetal biometrics were assessed on GD17.5.
RESULTS: Following DT treatment maternal baseline hemodynamics
were unchanged, however following L-NAME infusion, there was a
greater increase in MAP in Treg cell depleted mice (control:15.0±2.8%
increase, Foxp3-DTR: 23.4±1.7% increase, p=0.047). Uterine artery
hemodynamics were perturbed, with resistance and pulsatility indices
elevated by 15% and 20%, respectively. Uterine artery conversion of
bigET-1 to active ET-1 was enhanced following Treg cell depletion
(p<0.001). ET-1-induced constriction was unaffected. Serum proinflammatory cytokines, including TNF, were elevated (p=0.001). In late
pregnancy, fetuses from Treg cell deficient mice were growth restricted
(p=0.01).
CONCLUSION: We demonstrate an essential role for Treg cells
in maternal vascular adaptations to pregnancy. Given the severe
implications of preeclampsia on the future health of the mother and her
baby, investigation of therapeutic strategies targeting Treg cells offers a
promising intervention.

Scientific Abstracts

O-041
Can Maternal Vascular Lesions in the Placenta Predict Severity
and Recurrence of Hypertensive Disorders of Pregnancy? Alisse
Hauspurg†,2 Vanessa Assibey-Mensah,2 W Tony Parks,1 Arun Jeyabalan,2
James M Roberts,2 Janet Catov.2 1Dartmouth College, Hanover, NH,
United States; 2Magee-Womens Research Institute, University of
Pittsburgh, Pittsburgh, PA, United States.
INTRODUCTION: Women with hypertensive disorders of pregnancy
(HDP) have recurrence rates between 10-65% depending on disease
severity. A history of preterm, severe preeclampsia (PEC) affords the
highest recurrence risk. Women with HDP also have excess risk of
future cardiovascular disease (CVD). The most specific and chronic
placental vascular pathophysiologic feature of HDP is maternal vascular
malperfusion (MVM), characterized by incomplete vascular remodeling
and vascular findings comparable to atherosclerosis. We hypothesized that
the presence of MVM lesions is associated with both severity of HDP and
recurrence of PEC in future pregnancies.
METHODS: A retrospective cohort study of women with placental
pathology who delivered in 2008 to 2012 was performed using the
previously validated Magee Obstetrical Medical and Infant Database
(MOMI). Women with HDP including gestational hypertension (GH),
mild PEC, severe PEC and severe, preterm PEC were identified in the
MOMI database and compared to women without a diagnosis of a HDP.
A multinomial logistic regression model estimated the risk of HDP
associated with MVM lesions and adjusted for race, maternal diabetes,
and tobacco use.
RESULTS: 20,165 deliveries had complete pregnancy data and placental
pathology. We studied 1,070 women with more than one delivery
during the study period. MVM lesions were associated with severity of
HDP (p<0.0001). MVM lesions were found in 5,044 (32.8%) of nonhypertensives, 500/1328 (44.8%) of GH, 720/1607 (44.8%) of mild
PEC, 621/868 (71.5%) of severe PEC, and 477/590 (80.9%) of preterm
severe PEC. Recurrent preeclampsia was more common in women with
MVM lesions in their first pregnancy who, after adjusting for covariates
had a 54% (95%CI =1.04-2.28) increased risk of recurrent preeclampsia
compared to women with PEC and no MVM lesions in their initial
pregnancy.
CONCLUSION: MVM lesions are associated with HDP and occur
significantly more frequently in pregnancies with more severe HDP.
Further, women with evidence of MVM in their initial delivery had
an increased risk of recurrent preeclampsia. This may have valuable
implications not only for counseling and prediction of future pregnancy
outcomes but may facilitate early identification of women with a
pathologic vascular phenotype for primary prevention of CVD.
*Figure(s) will be available online.

O-042
Flow Mediated Dilation; the Effect of Aging in Women with a History
of Vascular Complicated and Uncomplicated Pregnancy. Veronica A
Lopes van Balen†,2 Chahinda Ghossein-Doha,2 Julia J Spaan,2 Sander MJ
van Kuijk,2 Arnold P Hoeks,1 Koen D Reesink,1 Marc EA Spaanderman*.2
1
Maastricht University, Maastricht, Netherlands; 2Maastricht University
Medical Centre, Maastricht, Netherlands.
INTRODUCTION: Arterial aging is a normal physiological process
that develops gradually over time. It is generally thought that, as part
of aging, vascular function decreases, which in turn, raises the risk of
cardiovascular disease. In women, vascular complicated pregnancy may
enhance this physiological aging process. Henceforth, we hypothesize
that vascular degeneration is more pronounced in women with a vascular
complicated pregnancy in their history.
METHODS: We evaluated women with a vascular complicated or
normotensive pregnancy in their history, part of a large cross-sectional
cohort study spanning 30 years after gestation. Endothelium dependent
arterial function was assessed by flow mediated dilation (FMD) of the
brachial artery, and endothelium independent dilation by sublingual
administered exogenous nitroglycerine (NG). To analyse the effect of
age on endothelial function a multivariable adjusted logistic regression
was performed.

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