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Lefty promotes trophoblast lineage specification in human placenta
SMFM Abstracts S127 397 LEFTY PROMOTES TROPHOBLAST LINEAGE SPECIFICATION IN HUMAN PLACENTA VISWANATHAN RAVISHANKAR1, KRISTIN PATZKOWSKI2, MEIYI TANG1, CECILIA AVILA3, PAUL OGBURN1, J. QUIRK4, SIAMAK TABIBZADEH1, 1State University of New York at Stony Brook, Obstetrics, Gynecology and Reproductive Medicine, Stony Brook, New York, 2State University of New York at Stony Brook, Department of Obstetrics, Gynecology and Reproductive Medicine, Stony Brook, New York, 3Columbia University, Obstetrics and Gynecology, Port Jefferson, New York, 4SUNY Stony Brook, Stony Brook, New York OBJECTIVE: Microarray analysis has shown a member of the TGF-beta super family, Lefty A, to be the single most abundant inhibitor in stem cells and in the maternal decidua that supports embryo implantation. Based on the foundation that Lefty is induced by the transcriptional factor Oct3/4 that regulates trophoectodermal differentiation, we hypothesized that Lefty is involved in placental development. We sought to determine the presence and distribution of Lefty in human Placenta and examine the biologic impact of lefty A in specification of trophoblasts. STUDY DESIGN: Placental samples were obtained from normal term pregnancies (cesarean or vaginal deliveries). Lefty mRNA was detected by reverse transcription followed by polymerase chain reaction (RT-PCR) and Lefty proteins by Western blot analysis. Immunoreactive Lefty was localized in tissue sections by immunohistochemical staining. Decidual cells and BeWo trophoblast cells were subjected to transduction with empty control adenovirus particles and with particles driving Lefty expression. Cells were harvested and analyzed by RT-PCR to determine trophoblast lineage specification and assessed for fusion. RESULTS: 1) Lefty was expressed in villous and extra-villous trophoblasts including binucleated cells. 2) Lefty transduction of maternal decidual cells derived from third trimester placenta led to the development of binucleation, expression of cytokeratin and CGbeta. 3) Transduction of BeWo cells by Lefty increase expression of trophoblast markers including, Imfa, and Stral3. 4) Lefty also led to increased number of multinucleated cells with a large size within 48 hr of treatment. CONCLUSION: The findings suggest a role for Lefty in cell-cell fusion and trophoblast fate specification.
399 THE CONTRIBUTION OF BLOOD GLUCOSE CONTROL TO THE DEVELOPMENT OF PREGNANCY-RELATED HYPERTENSION IN WOMEN WITH GESTATIONAL DIABETES VICTOR HUGO GONZALEZ-QUINTERO1, NIKI ISTWAN2, DEBBIE RHEA2, JENA CARTER1, M. CAMILLE HOFFMAN1, ANTOENETA MULLER1, LOREN SMARKUSKY1, AMANDA COTTER1, GARY STANZIANO2, 1University of Miami, Obstetrics and Gynecology, Miami, Florida, 2Matria Healthcare, Clinical Research, Marietta, Georgia OBJECTIVE: To examine if blood glucose (BG) control impacts the incidence of pregnancy-related hypertension (PRH) in women with gestational diabetes (GDM). STUDY DESIGN: Women enrolled for outpatient GDM management (patient education, counseling and daily review of blood glucose and urine ketone measurements) that delivered at term and who had documented A1c testing at R32 weeks were included. Maternal characteristics and neonatal outcome were compared between those that developed PRH and those that did not using the following statistical tests: Fisher’s Exact, Pearson’s or continuitycorrected Chi-square, and Mann-Whitney U. A neonatal composite outcome of one or more of the following: birth weight O4500 gms, large-forgestational-age, jaundice, neonatal hypoglycemia, or stillbirth was determined. The primary study outcome, incidence of PRH, was compared by A1c result at R32 weeks (!5, 5-5.9, 6-6.9, or R7). RESULTS: 1288 records of women with GDM meeting inclusion criteria were examined. The overall incidence of PRH was 8.7%. Women that developed PRH were more likely to be obese and have a higher A1c value than those without PRH (p!0.001 and (p=0.005, respectively). Infants from women with GDM and PRH compared to those with GDM only had a higher incidence of macrosomia O4500gms (4.5% vs. 1.6%, (p=0.051) and a higher incidence of the composite outcome, 36.6% vs. 26.4%, (p=0.020). The incidence of PRH by A1c value at R32 weeks is presented in table.
CONCLUSION: Inadequate blood glucose control may contribute to the development of PRH in women with GDM. Larger studies are needed to confirm our findings.
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.433
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.435
398 WEIGHT GAIN VELOCITY IN RELATION TO THE DEVELOPMENT OF GESTATIONAL HYPERTENSION AND OR PREECLAMPSIA VICTORIA BELOGOLOVKIN1, STEPHANIE ENGEL2, DAVID SAVITZ2, CAROL CHELIMO2, ANNA MARIA SIEGA-RIZ3, RHODA SPERLING1, 1Mount Sinai School of Medicine, Obstetrics, Gynecology and Reproductive Science, New York, New York, 2Mount Sinai School of Medicine, Department of Community and Preventive Medicine, New York, New York, 3University of North Carolina at Chapel Hill, Dept. of Maternal & Child Health, Dept. of Nutrition, Carolina Population Center, Chapel Hill, North Carolina OBJECTIVE: To evaluate the effect of wt gain trajectory during pregnancy on the incidence of gestational hypertension (PIH) and preeclampsia (PE). STUDY DESIGN: We conducted a nested case-control study of PIH (n = 565) and PE (n = 130) within the Pregnancy, Infection and Nutrition cohort. Cases were individually matched to controls on time at risk to a ratio of 1:3. Conditional logistic regression was used to evaluate the relationship between maternal wt gain in each trimester and risk of PIH and or PE, after adjustment for relevant covariates. The associated interactions between pre-pregnancy BMI and PIH or PE were similarly evaluated. RESULTS: The risk of PIH and PE increased in a dose-dependent manner with increasing wt gain in the 3rd trimester. However, wt gain in the 1st trimester increased the risk of PIH and PE after accounting for pre-pregnancy BMI. Increasing obesity carried increased risk of PIH and PE even at the median or less wt gain in the 1st trimester. However, an obese pre-pregnancy BMI coupled with greater than the median wt gain in the 1st trimester resulted in a multiplicative increase in risk. (Table) CONCLUSION: We found a dose dependent increase in risk of PIH and PE with increasing maternal wt gain in the third trimester. Interestingly, an effect was noted as early as the 1st trimester when BMI was considered. Therefore, in some circumstances, maternal wt gain may predict those at higher risk for PIH and PE as early as the 1st trimester. Risk of PIH and PE associated with 1st trimester weight gain accounting for pre-pregnancy BMI *P for interaction !0.05
!/=median wt gain O median wt gain
Normal BMI
Overweight
Obese
1.0 0.9 (0.6,1.3)
2.7 (1.5,4.9) 1.5 (0.8,2.8)
3.6 (2.3,5.5) 6.1 (3.6,10.3)*
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.434
400 CIRCULATING MATRIX METALLOPROTEINASE-2 CONCENTRATION IN PREGNANCIES COMPLICATED BY SMOKING VANITA DHARAN1, KRISTINE LAIN1, STACY MCGONIGAL1, JULIE DELOIA1, ARUNDHATHI JEYABALAN1, 1University of Pittsburgh, Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, Pennsylvania OBJECTIVE: Smoking during pregnancy is associated with many adverse pregnancy outcomes. Smoking is also associated with increased concentrations of matrix metalloproteinase-2 (MMP-2). Smoking and MMP-2 are also associated with endothelial dysfunction, atherosclerosis and aortic aneurysms. To date there have been no published studies evaluating the effect of smoking during pregnancy on circulating MMP-2 concentrations. In this study we sought to evaluate levels of circulating MMP-2 concentrations in pregnancies complicated by heavy smoking compared to nonsmokers. STUDY DESIGN: A nested case-control study was performed using plasma samples from a prospective cohort of nulliparous pregnant smokers and nonsmokers. Subjects were matched for gestational age, race, and BMI for a total of 24 heavy smokers and 48 nonsmokers. Heavy smokers were classified by plasma cotinine concentration R 100ng/ml and nonsmokers if cotinine concentration was !5ng/ml. Plasma MMP-2 concentrations were determined by enzyme-linked immunoabsorbant assay. Smokers and nonsmokers were compared using Mann-Whitney statistical analysis for two gestational age categories, second trimester (!26 weeks) and third trimester (R26 weeks). RESULTS: MMP-2 concentrations were significantly lower in heavy smoking nulliparous women compared to non smokers (p!0.05) in the third trimester. There were no significant differences in MMP-2 concentrations in the second trimester. CONCLUSION: Heavy smoking may contribute to lower circulating levels of MMP-2 in the third trimester of pregnancy. We speculate that MMP-2 may play a role in the vascular alterations of pregnancies complicated by heavy smoking. Plasma MMP-2 concentrations
!26 weeks R26 weeks
Non smokers (mean G SE)
Heavy Smokers (mean G SE)
285.1 G 11.1 323.7 G 12.8
275.9 G 18.1 274.0 G 18.6
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.436
399 THE CONTRIBUTION OF BLOOD GLUCOSE CONTROL TO THE DEVELOPMENT OF PREGNANCY-RELATED HYPERTENSION IN WOMEN WITH GESTATIONAL DIABETES VICTOR HUGO GONZALEZ-QUINTERO1, NIKI ISTWAN2, DEBBIE RHEA2, JENA CARTER1, M. CAMILLE HOFFMAN1, ANTOENETA MULLER1, LOREN SMARKUSKY1, AMANDA COTTER1, GARY STANZIANO2, 1University of Miami, Obstetrics and Gynecology, Miami, Florida, 2Matria Healthcare, Clinical Research, Marietta, Georgia OBJECTIVE: To examine if blood glucose (BG) control impacts the incidence of pregnancy-related hypertension (PRH) in women with gestational diabetes (GDM). STUDY DESIGN: Women enrolled for outpatient GDM management (patient education, counseling and daily review of blood glucose and urine ketone measurements) that delivered at term and who had documented A1c testing at R32 weeks were included. Maternal characteristics and neonatal outcome were compared between those that developed PRH and those that did not using the following statistical tests: Fisher’s Exact, Pearson’s or continuitycorrected Chi-square, and Mann-Whitney U. A neonatal composite outcome of one or more of the following: birth weight O4500 gms, large-forgestational-age, jaundice, neonatal hypoglycemia, or stillbirth was determined. The primary study outcome, incidence of PRH, was compared by A1c result at R32 weeks (!5, 5-5.9, 6-6.9, or R7). RESULTS: 1288 records of women with GDM meeting inclusion criteria were examined. The overall incidence of PRH was 8.7%. Women that developed PRH were more likely to be obese and have a higher A1c value than those without PRH (p!0.001 and (p=0.005, respectively). Infants from women with GDM and PRH compared to those with GDM only had a higher incidence of macrosomia O4500gms (4.5% vs. 1.6%, (p=0.051) and a higher incidence of the composite outcome, 36.6% vs. 26.4%, (p=0.020). The incidence of PRH by A1c value at R32 weeks is presented in table.
CONCLUSION: Inadequate blood glucose control may contribute to the development of PRH in women with GDM. Larger studies are needed to confirm our findings.
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.433
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.435
398 WEIGHT GAIN VELOCITY IN RELATION TO THE DEVELOPMENT OF GESTATIONAL HYPERTENSION AND OR PREECLAMPSIA VICTORIA BELOGOLOVKIN1, STEPHANIE ENGEL2, DAVID SAVITZ2, CAROL CHELIMO2, ANNA MARIA SIEGA-RIZ3, RHODA SPERLING1, 1Mount Sinai School of Medicine, Obstetrics, Gynecology and Reproductive Science, New York, New York, 2Mount Sinai School of Medicine, Department of Community and Preventive Medicine, New York, New York, 3University of North Carolina at Chapel Hill, Dept. of Maternal & Child Health, Dept. of Nutrition, Carolina Population Center, Chapel Hill, North Carolina OBJECTIVE: To evaluate the effect of wt gain trajectory during pregnancy on the incidence of gestational hypertension (PIH) and preeclampsia (PE). STUDY DESIGN: We conducted a nested case-control study of PIH (n = 565) and PE (n = 130) within the Pregnancy, Infection and Nutrition cohort. Cases were individually matched to controls on time at risk to a ratio of 1:3. Conditional logistic regression was used to evaluate the relationship between maternal wt gain in each trimester and risk of PIH and or PE, after adjustment for relevant covariates. The associated interactions between pre-pregnancy BMI and PIH or PE were similarly evaluated. RESULTS: The risk of PIH and PE increased in a dose-dependent manner with increasing wt gain in the 3rd trimester. However, wt gain in the 1st trimester increased the risk of PIH and PE after accounting for pre-pregnancy BMI. Increasing obesity carried increased risk of PIH and PE even at the median or less wt gain in the 1st trimester. However, an obese pre-pregnancy BMI coupled with greater than the median wt gain in the 1st trimester resulted in a multiplicative increase in risk. (Table) CONCLUSION: We found a dose dependent increase in risk of PIH and PE with increasing maternal wt gain in the third trimester. Interestingly, an effect was noted as early as the 1st trimester when BMI was considered. Therefore, in some circumstances, maternal wt gain may predict those at higher risk for PIH and PE as early as the 1st trimester. Risk of PIH and PE associated with 1st trimester weight gain accounting for pre-pregnancy BMI *P for interaction !0.05
!/=median wt gain O median wt gain
Normal BMI
Overweight
Obese
1.0 0.9 (0.6,1.3)
2.7 (1.5,4.9) 1.5 (0.8,2.8)
3.6 (2.3,5.5) 6.1 (3.6,10.3)*
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.434
400 CIRCULATING MATRIX METALLOPROTEINASE-2 CONCENTRATION IN PREGNANCIES COMPLICATED BY SMOKING VANITA DHARAN1, KRISTINE LAIN1, STACY MCGONIGAL1, JULIE DELOIA1, ARUNDHATHI JEYABALAN1, 1University of Pittsburgh, Obstetrics, Gynecology and Reproductive Sciences, Pittsburgh, Pennsylvania OBJECTIVE: Smoking during pregnancy is associated with many adverse pregnancy outcomes. Smoking is also associated with increased concentrations of matrix metalloproteinase-2 (MMP-2). Smoking and MMP-2 are also associated with endothelial dysfunction, atherosclerosis and aortic aneurysms. To date there have been no published studies evaluating the effect of smoking during pregnancy on circulating MMP-2 concentrations. In this study we sought to evaluate levels of circulating MMP-2 concentrations in pregnancies complicated by heavy smoking compared to nonsmokers. STUDY DESIGN: A nested case-control study was performed using plasma samples from a prospective cohort of nulliparous pregnant smokers and nonsmokers. Subjects were matched for gestational age, race, and BMI for a total of 24 heavy smokers and 48 nonsmokers. Heavy smokers were classified by plasma cotinine concentration R 100ng/ml and nonsmokers if cotinine concentration was !5ng/ml. Plasma MMP-2 concentrations were determined by enzyme-linked immunoabsorbant assay. Smokers and nonsmokers were compared using Mann-Whitney statistical analysis for two gestational age categories, second trimester (!26 weeks) and third trimester (R26 weeks). RESULTS: MMP-2 concentrations were significantly lower in heavy smoking nulliparous women compared to non smokers (p!0.05) in the third trimester. There were no significant differences in MMP-2 concentrations in the second trimester. CONCLUSION: Heavy smoking may contribute to lower circulating levels of MMP-2 in the third trimester of pregnancy. We speculate that MMP-2 may play a role in the vascular alterations of pregnancies complicated by heavy smoking. Plasma MMP-2 concentrations
!26 weeks R26 weeks
Non smokers (mean G SE)
Heavy Smokers (mean G SE)
285.1 G 11.1 323.7 G 12.8
275.9 G 18.1 274.0 G 18.6
0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.436