SRI Supplement to Reproductive Sciences - Volume 25 Number 1 - March 2018 - 238A

238A

Reproductive Sciences Vol. 25, Supplement 1, March 2018

Thus we conclude that inhibiting the mitochondrial ETC or activating
mitochondrial biogenesis offers new targets for potential therapeutics to
treat preeclampsia.

F-170
Abnormal Lymphangiogenesis is Associated with Decreased Decidual
Regulatory T Cells in Severe Preeclampsia. Yun Ji Jung,2 Yong-sun
Maeng,2 Hwa Jin Lee,2 Yejin Park,2 Jeeun Song,2 Young-Han Kim,2
JoonHo Lee,2 Yong Won Park,1,2 Ja-Young Kwon*.2 1Bundang Cheil
Women's Hospital, Sungnam, Korea, Republic of; 2Institute of Women's
Life Science, Yonsei University College of Medicine, Seoul, Korea,
Republic of.
INTRODUCTION: Lymphatic vasculature control lymphocyte
trafficking and limit adaptive immune response. In the previous
disease models, abnormal immune function leading to break down in
lymphangiogenesis was shown to take part in the disease pathophysiology.
Unbalanced immune cells, especially dysfunction of regulatory T cells
(Treg), in the maternal-fetal interface may be one cause of severe
preeclampsia(PE). Therefore, impaired lymphangiogenesis and Treg
regulation around placenta are theorized to contribute to the severe
PE pathophysiology, yet the current research on this field is limited.
This study aims 1) to localize lymphatic vessels in the placenta and the
membranes, 2) to compare the difference in lymphangiogenesis between
normal and severe PE, and 3) to investigate the association between
lymphangiogenesis and Tregs in severe PE.
METHODS: We used whole mount immunostaining of full-thickness
uterus and placenta from normal pregnant mice to identify the location
of lymphatic vessels. Next, we obtained fetal chorioamniotic membranes
containing decidua, and the chorionic plate from pregnant women with
PE (n=10) and gestational age mateched controls (n=10). To localize
the lymphatic vessels in placenta, immunofluorescence staining for
LYVE1 and CD31 was performed. To compare the development of
lymphatic vessels between normal and severe PE placenta, the number
of lymphatic vessels and the integrity of lymphatic endothelial cell
junction were analyzed. The distribution of Tregs was analyzed by
immunohistochemistry for CD4, CD25 and FOXP3. The number of
CD4+CD25+FOXP3+(Tregs) cells were quantified by counting stained
cells in six randomly selected fields per section.
RESULTS: In the uterus of normal pregnant mice, LYVE1-positive
lymphatic vessels were only present in the uterine wall. In human, LYVE1positive lymphatic vessels were abundance in decidua and seemed like
large tubular structure in normal. In contrast, in decidua of severe PE
showed a low density and small diameter of LYVE1-positive lymphatic
vessels. Furthermore, decreased lymphatic vessel density was correlated
with decreased number of decidual Tregs (r2=0.964).
CONCLUSION: Lymphatic vessels were localized at human decidua and
present low density and small diameter in severe PE compare with normal.
In addition, the number of decidual Treg was significantly decreased in
PE. These results suggest that abnormal lymphatic vessel development
in decidua during pregnancy may induce the deficiency in Tregs number
of decidua and associated with defective immune tolerance and severe
PE. *The research was supported by National Research Foundation of
Korea (NRF-2017R1D1A1B03029081).

Scientific Abstracts

ultrasound and continuous blood pressure assessment. We also evaluated
popliteal flow mediated vasodilation (FMD), aorto-femoral pulse wave
velocity (PWV) and cardiovascular response to volume challenge (500 mL
LR) as additional measures of vascular function. Subjects with subsequent
pregnancies (n=64) were monitored for developing hypertension including
gestational hypertension (GTH, n=9) or preeclampsia (PRE, n=6). Data
are expressed as the median and interquartile range. Spearman correlation
coefficients were employed to determine significant associations.
RESULTS: Age was not significantly different between those who
developed HTN compared to women who remained normotensive (NL)
however BMI was higher in the HTN group (mean BMI 27.9 ± 6.2 kg/m2
versus 23.1 ± 4.5 kg/m2, p=0.001). Median β-stiffness index was higher in
women who developed any hypertension (median = 16.85, IQR = 13.02 29.93) vs. NL (median =13.49, IQR= 9.7 - 17.23). Median distensibility
was lower in the hypertension group than the non-hypertension group
(median = 0.6, IQR = 0.37 - 0.87) vs. (median = 0.82, IQR = 0.59 1.17). Spearman correlation coefficients showed that β-stiffness and
Distensibility both correlate with heart rate response to volume challenge
(β-stiffness r=-0.23, p=.02 and distensibility r=0.23, p=.03). β-stiffness
and distensibility were not significantly associated with PWV or FMD.
CONCLUSION: Simple non-invasive measurements such as popliteal
artery ultrasound, blood pressure and electrocardiography assessment
may be useful to calculate indices of vessel compliance that predict risk
of developing hypertension during pregnancy. Furthermore, the lack
of correlation between stiffer vessels, as assessed by β-stiffness and
distensibility and either FMD or PWV may suggest that there are several
unique measures of vessel function that contribute to the development of
hypertension in pregnancy.

F-172
Higher Women's Cardiovascular Mortality in Their Forties Years
after Hypertensive Disease of Pregnancy. Sophie Welters†,3 Pim
Teunissen,3 Lisa Alma,3 Wietske Hermes,2 Anita Ravelli,1 Christianne
De Groot.3 1Amsterdam Medical Center, Amsterdam, Netherlands;
2
Haaglanden Medical Center, The Hague, Netherlands; 3VU Medical
Center - Amsterdam, Amsterdam, Netherlands.
INTRODUCTION: Hypertensive pregnancy disorders are described as a
stress test providing a warning for development of cardiovascular disease.
Therefore, hypertensive pregnancy disorders might be of predictive value
to trace cardiovascular vulnerability at a relatively young age with a
higher mortality risk as sequel. To test this hypothesis we analyzed the
association of women with hypertensive pregnancy disorders and death
due to cardiovascular disease, using a national cohort of consecutive
women who delivered in the Netherlands.
METHODS: Women who gave birth during 1995 - 2015 and were
registered in the National Birth Registry of the Netherlands were analyzed
for death due to cardiovascular disease through linkage with the National
Death Registry. Cardiovascular death was analyzed in women with a
history of hypertensive pregnancy disorders compared to uncomplicated
pregnancies using relative risk ratios.
RESULTS: Of 1.615.323 women with a mean age of 40.6 years, 1537
(0.1%) died due to cardiovascular disease. Preeclampsia, pregnancy
induced hypertension and recurrent preeclampsia were associated with a
higher risk of cardiovascular mortality (table 1).

F-171
Popliteal Artery Stiffness in Nulliparous Women is Associated with
Hypertension in Pregnancy. Alexandra Miller†, Kylie M Cooper, Erin
A Morris, Carole McBride, Gary J Badger, Ira M Bernstein*. University
of Vermont, Burlington, VT, United States.
INTRODUCTION: The maternal physiological challenge of pregnancy
requires profound maternal cardiovascular adaptations. We hypothesized
that vascular function assessed prior to pregnancy, with a focus on vessel
stiffness, would predispose women to developing hypertension (HTN)
during pregnancy.
METHODS: In a prospective study, we assessed 107 nulliparous,
predominately white, women aged 18 to 41 years, with an average BMI
of 24.0 ± 4.6 kg /m2 (mean ± s.d.). Popliteal artery stiffness (β-stiffness)
and distensibility were measured during the follicular phase using Doppler

Table 1: Cardiovascular mortality
Women with

Cardiovascular mortality
OR; 95% CI

Preeclampsia vs no preeclampsia

2.56; 95% CI 2.15 - 3.04

Recurrent preeclampsia (>1) vs no preeclampsia

3.12; 95% CI 1.67 - 5.18

Pregnancy induced hypertension vs no
hypertensive pregnancy disorder

2.39; 95% CI 2.09 - 2.73

Women with preeclampsia did not die at younger age (40.6 vs. 41.1 years;
p=0.994) or within a shorter time after first birth (8.70 vs. 8.73 years;
p=0.80) compared to women without preeclampsia. The main causes of
cardiovascular mortality in women with a history of preeclampsia were
cerebrovascular disease (38.1%) and ischemic heart disease (16.4%).

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