Poster Session I ajog.org

especially DNA, is indicative of a novel pathophysiologic mechanismassociated with PTB and pPROM. The study purpose was toexamine the OS effects in inducing protein and DNA damage andsenescence in an animal model of OS induced by cigarette smokeextract (CSE).STUDY DESIGN: CD-1 mice (n¼5/group) on day 14 of gestation wereallocated to CSE diluted in saline, saline as a control, SB 203580 (ap38 mitogen-activated protein kinase (MAPK) inhibitor) or acombination, injected into the uterine horn between gestational sacs.Mice were sacrificed on day 18, and amniotic sacs were collected.Protein and DNA damage were evaluated by immunostaining for 3-Nitrotyrosine modified proteins (3-NT) and phosphorylatedgamma-histone2A (ɣ-H2AX), respectively. Activation of prosen-escence mitogen-activated protein kinase (p38MAPK) and p53 wasevaluated by Western blot, and the data were analyzed by ANOVAand Tukey’s test, p < 0.05 was used for significance.RESULTS: Amniotic cells from CSE-treated animals showed signifi-cant OS compared to saline only as indicated by 3-NT staining. Theɣ-H2AX staining was also increased in CSE-treated samplescompared to controls, demonstrating DNA damage foci formation.Western blot analysis revealed significant activation of phosphory-lated p38MAPK by CSE, which was reduced after treatment withSB203580. Activation of prosenescence marker p53 was not observedin the amniotic sac tissue.CONCLUSION: Oxidative stress, induced by CSE, results in protein andDNA damage and p38MAPK activation, indicating prematuresenescence in the amniotic cells, as previously observed in in vitrostudies. Prevention of p38MAPK activation can be a novel approachto prevention of preterm birth and other adverse pregnancy out-comes related to premature senescence.

Figure 1. Amniotic sac from CD-1 pregnant mice. A. 3-Nitro-tyrosine modified proteins (3-NT) staining. B. Pronounced ɣH2AXimmunofluorescence staining after CSE treatment. Bar graph rep-resents the percentage of positive cells. C. Immunoblot of phos-phorylated, total p38 mitogen-activated kinase (MAPK) and b-actinprotein; Bar graphs demonstrate quantitation of Western blot banddensities normalized to b-actin levels. (CSE: water soluble cigarettesmoke extract; SB: SB203580 p38MAPK inhibitor; CTR: control).*Anova, p<0.05.

171

Sex-dependent metabolic abnormalities in maternalbisphenol a (BPA)-exposed offspringJuanita Jellyman1, Michael Ross1, Mina Desai11Los Angeles Biomedical Reseach Institute at Harbor-UCLA Medical Center,Department of Obstetrics and Gynecology, Torrance, CAOBJECTIVE: The use of plastics (e.g. water bottles) containing theendocrine disrupter BPA has accelerated in parallel to obesity rates.BPA is detectable in plasma of pregnant women, and concentrated infetal plasma and amniotic fluid. As early BPA exposure may alterfetal development, we determined the effects of in utero BPA onoffspring cardiovascular and metabolic development.

S100 American Journal of Obstetrics & Gynecology Supplement to JANUARY

STUDY DESIGN: Two weeks prior to mating, and throughout preg-nancy and lactation, rat dams had ad libitum access to filtereddrinking water (control) or drinking water containing 5 mg/L BPA.After birth, litter size was standardized and pups nursed by the samedam until weaning, after which no further BPA exposure occurred.At 3 weeks of age, offspring body composition was determined(DEXA) and basal plasma profiles of glucose (HemoCue GlucoseAnalyzer), insulin and triglyceride concentrations (ELISA) weredetermined. Glucose tolerance and arterial blood pressure wereevaluated at 6 weeks of age.RESULTS: Despite normal birth weight, at 3 weeks of age BPA malesand females had increased body weight (53�1 vs 46�2 and 51�2 vs43�3 g, respectively; P<0.05) and fat mass (9.7�1.4 vs 6.6�0.7 and9.8�1.vs 5.1�0.3 g; P<0.05). Further, maternal BPA induced sex-specific effects on offspring metabolism and cardiovascular function.Male BPA-offspring exhibited increased area under the glucoseclearance curve (5693�911 vs 2900�686 mg.dL-1min-1; P<0.05) aswell as increased systolic blood pressure (148�2 vs 131�3 mmHg;P<0.05), whereas female BPA-offspring showed hyper-triglyceridemia (33.7�3.3 vs 13.7�3.0 mg/dL; P<0.05). There wereno differences in basal plasma concentrations of glucose or insulinbetween control and BPA-offspring.CONCLUSION: Maternal BPA induces sex-dependent metabolic ab-normalities. BPA males are glucose intolerant and hypertensive,while BPA females are hypertriglyceridemic. Together with humanstudies, these findings suggest that maternal BPA exposure should belimited during pregnancy and lactation.

172

Insulin detemir in pregnancy: does it cross theplacenta?Katarzyna Suffecool3, Barak Rosenn1, Eric Niederkofler4,Urban Kiernan4, Janelle Foroutan1, Gideon Koren21St. Luke’s-Roosevelt Hospital Center, OB/GYN, New York, NY, 2TheHospital for Sick Children, Division of Pharmacology, Toronto, ON, Canada,3North Shore University Hospital, Manhasset, NY, 4Thermo Fisher Scientific,Tempe, AZOBJECTIVE: Insulin Detemir (IDet), a relatively new long acting in-sulin analogue, is currently being used in pregnancy, but its ability tocross the placenta is unknown. The objective of this study was todetermine if IDet is present in the fetal circulation in pregnantwoman treated with IDet.STUDY DESIGN: Pregnant women with gestational diabetes (GDM) ortype 2 diabetes treated with IDet were included in this prospectiveobservational study. Immediately post-delivery, maternal and um-bilical venous blood samples were obtained and centrifuged andplasma was frozen at -20c. Human insulin and IDet were measuredusing the Thermo Scientific� Mass Spectrometric ImmunoassayInsulin Workflow, combining immuno-capture of insulin analogueswith an anti-insulin antibody, and liquid chromatography-massspectrometric detection to enable sensitive detection of multipleinsulin analogues. Limits of detection of IDet was 50Pm, and 2pMfor human insulin. Statistical analysis included Pearson’s correlationcoefficient (rho).RESULTS: We studied 16 pregnant woman-neonate pairs (11 withGDM and 5 with type 2 diabetes) who were treated with IDet. Totalmaternal daily doses of IDet ranged between 10-96u (mean� SD57.7�-28.3u) divided into 2 doses administered every 12 hours.-There was no correlation between maternal IDet dose and resultantmaternal plasma concentrations (rho¼ 0.26, p¼0.43). Maternal andumbilical cord IDet and human insulin plasma concentrations at thetime of delivery are presented in the Table. IDet concentrations werebelow the level of detection (<50pM) in all 16 umbilical cord bloodsamples. None of the16 infants experienced neonatal hypoglycemia.CONCLUSION: IDet does not appear to cross the term human placenta,supporting emerging evidence of its fetal safety.

2015