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369: Progesterone receptor membrane component 1 and fas expression in peripheral blood mononuclear cells during pregnancy
Poster Session II
ajog.org
Pregnancy outcomes in pregnancies with GBS PCR intrapartum vs culture at 36 weeks
NDD: neonatal developmental disease QALY: quality adjusted life year GBS: group b streptococcus
369 Progesterone receptor membrane component 1 and fas expression in peripheral blood mononuclear cells during pregnancy
Nerlyne Desravines2, Geeta Swamy2, Sarahn Wheeler2, Brian Antczak2, Kent Weinhold1, Janet Staats1, Amy Murtha2 1 Duke University, Surgery, Durham, NC, 2Duke University, Ob/Gyn, Durham, NC
OBJECTIVE: Progestin therapy reduces the risk for preterm birth but
mechanisms responsible for this effect are not defined. Progesterone is known to alter immune cell function including induction of apoptosis in monocytes. Progesterone receptor membrane component 1 (PGRMC1) expression in Peripheral Blood Mononuclear cells (PBMC) has been described outside of pregnancy but not during pregnancy. Our objectives were to determine if PGRMC1 is expressed in PBMCs from pregnant women throughout gestation and if PGRMC1 expression is correlated with apoptosis as measured by Fas receptor expression. STUDY DESIGN: 30 pregnant women were enrolled in a prospective cohort study with blood samples collected serially throughout gestation. PBMC analysis was performed on 5 subjects (one sample/ trimester; n¼15). Polychromatic flow cytometry was used to measure expression of PGRMC1 and Fas on NK+, T, B cells, and Monocytes. Mean fluorescent intensity (MFI) was used to determine Fas expression and calculate the Antibody Binding Capacity (ABC) of PGRMC1. RESULTS: PGRMC1 is expressed in all cell types but highest in monocytes. Both PGRMC1 (ABC) (Figure A) and Fas (MFI) did not vary by trimester. PGRMC1 and Fas expression did not correlate within specific cell types but there was a positive correlation between PGRMC1 and Fas expression when all cell types were combined (r¼.72, P¼.0001)(Figure B). PGRMC1 and Fas expression correlation varied by trimester with the maximum correlation in the 3rd trimester (r¼0.82, p¼0.0001). CONCLUSION: Our results demonstrate PGRMC1 expression in PBMCs during pregnancy; highest in monocytes. While PGRMC1 was not different by trimester, trends toward increased expression in the second trimester were present. Importantly, there was a strong positive correlation between PGRMC1 and Fas receptor expression, a marker of apoptosis. This relationship may account for progesterone’s role in altering immune cell function during pregnancy and deserves further study.
370 Montelukast, a leukotriene receptor antagonist, inhibits spontaneous but not oxytocin-induced uterine contractions
Nevert Badreldin1, Stephanie Pierce1, Jennifer Gilner1, Leo Brancazio1, Chad Grotegut1 1
Duke University, Obstetrics and Gynecology, Durham, NC
OBJECTIVE: Montelukast is a leukotriene receptor antagonist used to
control asthma symptoms by inhibiting bronchiole smooth muscle contraction and by decreasing airway inflammation. Leukotrienes are known to increase uterine contractility and the uterus contains cysteinyl leukotriene receptor 1, the target for montelukast. Furthermore, recent work suggests that montelukast may decrease spontaneous uterine contractions, but its role in inhibiting oxytocininduced contractions is not known. Using a murine model, we sought to determine if montelukast affects oxytocin-induced uterine contractions. STUDY DESIGN: Uterine horns were isolated from non-pregnant wildtype C57BL/6J female mice and suspended in a tissue organ bath that measures contraction force. The effect of montelukast on spontaneous and oxytocin-induced uterine contractility was measured. Dose response curves were constructed using nonlinear regression and the best fit curves compared between treatment groups and vehicle. RESULTS: Six mice were utilized for each treatment group. Montelukast significantly decreased spontaneous uterine contractility in a dose-dependent fashion to 49% of baseline compared to 63% of baseline in vehicle treated horns (p¼0.045, Figure 1) at the highest tested dose (1 mM). In contrast, there was no difference in uterine contractility in response to oxytocin treatment (1nM to 100nM) among strips pre-treated with montelukast or vehicle control ([1 mM], 405% vs. 377% of baseline, p¼0.59, Figure 2). CONCLUSION: Montelukast is a leukotriene receptor antagonist that decreases spontaneous uterine contractility but not oxytocininduced uterine contractility in a murine model. As this agent also has anti-inflammatory properties, future work is needed to determine if montelukast can prolong pregnancy among women at high risk for preterm labor.
Figure 1: Effect of montelukast on spontaneous uterine contractions
S194 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
ajog.org
Pregnancy outcomes in pregnancies with GBS PCR intrapartum vs culture at 36 weeks
NDD: neonatal developmental disease QALY: quality adjusted life year GBS: group b streptococcus
369 Progesterone receptor membrane component 1 and fas expression in peripheral blood mononuclear cells during pregnancy
Nerlyne Desravines2, Geeta Swamy2, Sarahn Wheeler2, Brian Antczak2, Kent Weinhold1, Janet Staats1, Amy Murtha2 1 Duke University, Surgery, Durham, NC, 2Duke University, Ob/Gyn, Durham, NC
OBJECTIVE: Progestin therapy reduces the risk for preterm birth but
mechanisms responsible for this effect are not defined. Progesterone is known to alter immune cell function including induction of apoptosis in monocytes. Progesterone receptor membrane component 1 (PGRMC1) expression in Peripheral Blood Mononuclear cells (PBMC) has been described outside of pregnancy but not during pregnancy. Our objectives were to determine if PGRMC1 is expressed in PBMCs from pregnant women throughout gestation and if PGRMC1 expression is correlated with apoptosis as measured by Fas receptor expression. STUDY DESIGN: 30 pregnant women were enrolled in a prospective cohort study with blood samples collected serially throughout gestation. PBMC analysis was performed on 5 subjects (one sample/ trimester; n¼15). Polychromatic flow cytometry was used to measure expression of PGRMC1 and Fas on NK+, T, B cells, and Monocytes. Mean fluorescent intensity (MFI) was used to determine Fas expression and calculate the Antibody Binding Capacity (ABC) of PGRMC1. RESULTS: PGRMC1 is expressed in all cell types but highest in monocytes. Both PGRMC1 (ABC) (Figure A) and Fas (MFI) did not vary by trimester. PGRMC1 and Fas expression did not correlate within specific cell types but there was a positive correlation between PGRMC1 and Fas expression when all cell types were combined (r¼.72, P¼.0001)(Figure B). PGRMC1 and Fas expression correlation varied by trimester with the maximum correlation in the 3rd trimester (r¼0.82, p¼0.0001). CONCLUSION: Our results demonstrate PGRMC1 expression in PBMCs during pregnancy; highest in monocytes. While PGRMC1 was not different by trimester, trends toward increased expression in the second trimester were present. Importantly, there was a strong positive correlation between PGRMC1 and Fas receptor expression, a marker of apoptosis. This relationship may account for progesterone’s role in altering immune cell function during pregnancy and deserves further study.
370 Montelukast, a leukotriene receptor antagonist, inhibits spontaneous but not oxytocin-induced uterine contractions
Nevert Badreldin1, Stephanie Pierce1, Jennifer Gilner1, Leo Brancazio1, Chad Grotegut1 1
Duke University, Obstetrics and Gynecology, Durham, NC
OBJECTIVE: Montelukast is a leukotriene receptor antagonist used to
control asthma symptoms by inhibiting bronchiole smooth muscle contraction and by decreasing airway inflammation. Leukotrienes are known to increase uterine contractility and the uterus contains cysteinyl leukotriene receptor 1, the target for montelukast. Furthermore, recent work suggests that montelukast may decrease spontaneous uterine contractions, but its role in inhibiting oxytocininduced contractions is not known. Using a murine model, we sought to determine if montelukast affects oxytocin-induced uterine contractions. STUDY DESIGN: Uterine horns were isolated from non-pregnant wildtype C57BL/6J female mice and suspended in a tissue organ bath that measures contraction force. The effect of montelukast on spontaneous and oxytocin-induced uterine contractility was measured. Dose response curves were constructed using nonlinear regression and the best fit curves compared between treatment groups and vehicle. RESULTS: Six mice were utilized for each treatment group. Montelukast significantly decreased spontaneous uterine contractility in a dose-dependent fashion to 49% of baseline compared to 63% of baseline in vehicle treated horns (p¼0.045, Figure 1) at the highest tested dose (1 mM). In contrast, there was no difference in uterine contractility in response to oxytocin treatment (1nM to 100nM) among strips pre-treated with montelukast or vehicle control ([1 mM], 405% vs. 377% of baseline, p¼0.59, Figure 2). CONCLUSION: Montelukast is a leukotriene receptor antagonist that decreases spontaneous uterine contractility but not oxytocininduced uterine contractility in a murine model. As this agent also has anti-inflammatory properties, future work is needed to determine if montelukast can prolong pregnancy among women at high risk for preterm labor.
Figure 1: Effect of montelukast on spontaneous uterine contractions
S194 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015