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www.AJOG.org Hypertension/Physiology Oral Concurrent Session 6

but this trend was not significant in males (nicotine, n�6; control,n�9). Sucrose intake, total cholesterol, low-/very low-density lipo-proteins and triglyceride concentrations were similar between groupsin both males and females. Both nicotine-exposed males and femaleshad significantly lower high-density lipoprotein (HDL) concentra-tions than their control counterparts (males: 75.8 �/�3.9 vs. 92.7�/� 4.1 ng/dL; females: 60.9 �/� 2.2 vs. 75.3 �/� 3.8 ng/dL).CONCLUSION: Perinatal nicotine exposure is associated with signifi-cantly decreased HDL cholesterol levels in both male and female off-spring, and this effect is independent of adiposity and feeding pat-terns. These findings provide further evidence that female offspringexposed to nicotine during perinatal development are at increased riskfor cardiovascular disease compared to controls.

65 Maternal obesity programs offspring hypertensionia adipose renin-angiotensin system

Cristiane Guberman1, Guang Han1, Michael Ross1, Mina Desai1

1LABioMed at Harbor-UCLA Med. Ctr., Obstetrics and Gynecology,orrance, CA

OBJECTIVE: Maternal obesity programs an increased risk of offspringbesity and systemic hypertension. Although renal renin-angiotensinystem (RAS) is known to regulate blood pressure, it is now recog-ized that RAS is also activated in adipose tissue during obesity. An-iotensinogen (AGT) is the only known precursor of the vasoactiveeptide angiotensin II (AngII), which mediates vasopressor effects via

ts type 1 receptor (AT1). We hypothesized that programmed off-pring hypertension is dependent upon enhanced adipose tissue RASn offspring of obese rat dams.

STUDY DESIGN: At 3 week of age, female rats were weaned to high fat(HF: 60% k/cal) or (control, 10% k/cal) diet. At 11 weeks of age, theserats were mated and continued on their respective diets during preg-nancy. After birth, litter size was standardized, pups cross-fostered tocontrol dams and weaned to normal diet. At 6 months of age, body fat(DEXA) and blood pressure (tail-cuff) were measured. Thereafter,subcutaneous and retroperitoneal adipose tissue was harvested frommale offspring. Protein expression (Western Blot) of AGT and AT1was determined and normalized values presented as fold change.RESULTS: At 1 day and 6 months of age, HF had comparable body

eights, but markedly increased body fat (26�3 vs 18�2 %) andlood pressure (148�4 vs 135�4 mm Hg) as compared to Controls.n analysis of adipose tissue, HF offspring demonstrated significantlyncreased AGT (4-fold) and AT1 (6-fold) expression in retroperito-eal, though not subcutaneous adipose tissue.

CONCLUSION: Despite having comparable body weights, offspring ofHF-fed dams are obese, hypertensive and exhibit upregulated retro-peritoneal adipose AGT and AT1. These findings suggest that pro-grammed adiposity and adipose tissue enhanced RAS may contribute

HDL concentration (ng/dL) in control vs. nicotine-exposed male (left panel) and female (right panel)offspring.

to hypertension in offspring of obese/HF dams.

Supplem

66 MicroRNA expression profiles in firstrimester trophoblast of pregnanciesestined to develop severe preeclampsia

Krishna Singh1, Lindsay Spurka2, Jordon Brown2,incent Funari3, Siegfried Rotmensch4

1Cedars-Sinai Medical Center, Division of Maternal-Fetal Medicine,epartment of Obstetrics and Gynecology, Los Angeles, CA, 2Medicalenetics Institute at Cedars-Sinai Medical Center, Genomics Core, Losngeles, CA, 3Cedars-Sinai Medical Genetics Institute, David Geffen Schoolf Medicine at UCLA, Division of Medical Genetics and Biomedical Sciences,epartment of Pediatrics, Los Angeles, CA, 4Cedars-Sinai Medical Center,avid Geffen School of Medicine at UCLA, Division of Maternal-Fetaledicine, Department of Obstetrics and Gynecology, Los Angeles, CA

OBJECTIVE: Studies on 1st trimester trophoblast suggest differentialene expression in severe preeclampsia (SP). MicroRNAs (miRNA)odulate gene expression and unique signatures have been identified

n placental trophoblast at advanced gestations. We examinedhether miRNA is differentially expressed in first trimester tropho-last of pregnancies destined to develop severe preeclampsia.

STUDY DESIGN: 1st trimester trophoblast was prospectively collectedfrom women undergoing CVS at 10-13 wks gestation for prenatal diag-nosis. Samples were stored in RNAlater at -80 °C. Clinical informationwas obtained from designated patient questionnaires and medical re-cords. SP was diagnosed by ACOG criteria. Singleton SP cases (n�5) andnormal controls (n�5) were matched for maternal age, ethnicity, parity,gestational age at CVS, and fetal sex (only females) and comorbiditieswere excluded. Each RNA sample was processed with the FlashTa BiotinHSR RNA Labeling Kit For Affymetrix GeneChip miRNA Arrays andwere hybridized to GeneChip miRNA 3.0 Arrays. miRNA expression wasnormalized and then analyzed using Expression Console with RMA �DABG respectively.RESULTS: Mean gestational age at delivery was 36.9wks (range 29.040.0wks) and 39.6wks (range37.4-40.4 wks) for SP and normal controls,espectively. Principal component analysis revealed that most of the mo-ecular signatures are similar (Figure). Of the 1438 miRNAs analyzed, 576ere expressed in controls vs. 588 in SP. Supervised analysis of mi-RNA

xpression including a 2-way Wilcoxon T-Test showed that 24 miRNAsre significantly upregulated among SP vs controls, 5 with �1.5 foldhange. Some of the upregulated mi-RNAs regulate matrix metallopro-einases and genes for apoptosis, cellular movement and growth.

CONCLUSION: 1st trimester trophoblast from pregnancies destined todevelop SP display differential expression of miRNAs, which may beinstrumental in the pathophysiology of SP by affecting trophoblastinvasion into the placental bed.

ent to JANUARY 2013 American Journal of Obstetrics & Gynecology S39