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A comparative morphometric evaluation of normotensive and pre-eclamptic placenta from South African pregnant women
A54
Abstracts / Placenta 36 (2015) A1eA60
protease with high expression during placental development in the mouse, rhesus monkey and human. In the human placenta, HtrA3 exists as long (HtrA3-L) and short (HtrA3-S) isoforms; they are identical except HtrA3-L has an extra C-terminal domain (the PDZ domain). Placental HtrA3 is secreted into the maternal circulation with its serum profile reflecting placental production. We have previously reported in a small cohort of samples that serum HtrA3 levels at the end of first trimester significantly differed between women who subsequently proceeded with normal pregnancy and who developed preeclampsia. In this study, using highly specific HtrA3 monoclonal antibodies that were generated in our laboratory, we established and fully validated ELISAs suitable for the detection of total HtrA3 and HtrA3-L in human serum. We then conducted a retrospective study to determine serum HtrA3 at 11e13 weeks of gestation in a cohort of singleton pregnancies that subsequently proceeded with normal pregnancy (control n ¼ 292), or were complicated with preeclampsia (n ¼ 41) or small for gestational age (SGA, n ¼ 71). Compared to controls, SGA pregnancies showed significantly lower levels of total HtrA3, with no difference in HtrA3-L. In contrast, HtrA3-L level was significantly higher in the preeclamptic cases compared to controls, with no difference in total HtrA3. In addition, early-onset preeclampsia, which occurs before 34 weeks of gestation, showed significantly lower ratio of HtrA3-L over total HtrA3 compared to the control group. These data support the potential utility of serum HtrA3 for the early detection of preeclampsia and SGA.
P2.53. A COMPARATIVE MORPHOMETRIC EVALUATION OF NORMOTENSIVE AND PRE-ECLAMPTIC PLACENTA FROM SOUTH AFRICAN PREGNANT WOMEN Kaminee Maduray, Jagidesa Moodley, Thajasvarie Naicker. University of KwaZulu-Natal, Durban, South Africa In sub-Saharan Africa, pre-eclampsia is one of the major direct causes of maternal mortality. The pathology of pre-eclampsia is not fully understood. However, delivery of the placenta resolves all clinical symptoms and signs. The placenta is therefore a vital organ in understanding the pathogenesis of pre-eclampsia. Objective: The aim of this study was to compare placentae morphometrics between normotensive and pre-eclamptic pregnancies. Methods: Placentae were collected from normotensive (n ¼ 30) and preeclamptic (n ¼ 30) pregnancies. At delivery, each placenta was photographed and analysed for variations in gross appearance, abnormalities, point of insertion of umbilical cord as well as thickness. The placental images were further analysed for placental volume and diameter with the Zeiss Axiovision Rel. 4.8 software. Results: Placentae of pre-eclamptic pregnancies showed more abnormalities with regards to shape and the presence of oedema compared to the normotensive group. Eccentric insertion of the umbilical cord was predominate in the normotensive (60%) compared to the pre-eclamptic (45%) group. Marginal insertion of the umbilical cord was found in 27% and 28% of the normotensive and pre-eclamptic group respectively; whilst central insertion was noted in 13% of the normotensive and 10% in the pre-eclamptic group. Velamentous insertion occurred in the preeclamptic (17%) but was absent in the normotensive pregnancies. The mean placental weight, thickness, diameter and volume in the normotensive group were 675 g, 1.6 cm, 27 cm and 1024 cm3 respectively; and those in the pre-eclamptic group were 577 g, 1.5 cm, 25 cm and 743 cm3 the respectively. Conclusion: This study concludes that the mean placental weight, thickness, diameter and volume were significantly lower in pre-eclampsia compared to normotensive pregnancies.
P2.54. DOWN-REGULATION OF PLACENTAL GLUCOSE TRANSPORTER (GLUT)-1 IN PRE-ECLAMPSIA Camilla Marini 2, 4, Xiao Messerli 1, 2,
Benjamin Huang 3, 4,
P.
€ rgerLüscher 1, 2, Marianne Jo Jürg Gertsch 3, Matthias A.
Hediger 3, Christiane Albrecht 3, Daniel V. Surbek 1,2, Marc U. Baumann 1, 2. 1 Department of Obstetrics and Gynecology, University Hospital of Bern, Bern, Switzerland; 2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern, Bern, Switzerland; 3 Institute for Biochemestry and Molecular Medicine, University of Bern, Bern, Switzerland; 4 Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland Transplacental fetal glucose supply is predominantly regulated by glucose transporter-1 (GLUT1). Altered expression and/or function of GLUT1 may affect the intrauterine environment, which could compromise fetal development and could potentially lead to fetal programming. Until now it is unknown if placental GLUT1 is affected by pre-eclampsia (PE), a disease known to be associated with gestational diabetes (GDM) and IUGR. We therefore aimed to address the hypothesis that PE leads to altered expression and function of GLUT1. Placentae were obtained after elective caesarean sections following normal pregnancy and from pregnancies affected by PE. Syncytial basal membrane (BM) and apical microvillus membrane (MVM) fractions were prepared from syncytiotrophoblast (STB). GLUT1 protein expression was assessed by Western blot analysis and mRNA levels were quantified by qPCR. Radiolabeled glucose up-take assay, using placental-derived syncytial microvesicles and a transepithelial transport model using primary cytotrophoblasts were established to determine glucose transport activity. GLUT1 protein expression was significantly down-regulated in PE placentae compared to control placentae, while mRNA expression was unchanged. Glucose up-take into syncytial microvesicles was significantly reduced in PE compared to control. In a transepithelial transport model, phloretin-mediated inhibition of GLUT1 at the apical side of primary cytotrophoblast cells showed a significant shift of the transepithelial glucose transport. Our study shows for the first time that in PE, placental GLUT1 is downregulated on protein level and that GLUT1-mediated glucose transport activity is decreased. These suggest that GLUT1 might contribute to the pathogenetic link between PE and GDM, and eventually IUGR. Further, these data show that in PE GLUT1-mediated transplacental glucose transport is regulated on the apical side of the STB. Our results help to elucidate the role of GLUT1 in PE and to develop strategies to modulate glucose transport, aiming to reduce the risk for metabolic and cardiovascular diseases for the child later in life.
P2.55. PLACENTAL PATHOLOGIC FEATURES OF FETAL GROWTH RESTRICTION AND PREECLAMPSIA IN PRETERM: ARE PLACENTAL LESIONS DIFFERENT? Kylie Hae-Jin Chang, Ji-Hee Sung, Suk-Joo Choi, Soo-Young Oh, Jung-Sun Kim, Cheong-Rae Roh, Jong-Hwa Kim. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Objectives: Fetal growth restriction (FGR) and preeclampsia (PE) associate with increased neonatal morbidity, which occasionally accompany simultaneously. Altered normal placenta function and distorted structure is considered the most important pathological cause in both cases. This study aims to investigate the placental pathologic finding related to FGR and PE in preterm, by comparison. Methods: Preterm placenta (<35 weeks) from FGR (n ¼ 16), severe PE (n ¼ 16), both FGR and severe PE (n ¼ 20) and control pregnancies (n ¼ 30) were studied. Gestational age at delivery was equally matched between four groups. FGR was defined as fetal growth less than 5th percentile for gestational age and patients with chronic hypertension were excluded from the study population. Control group was composed of patients who delivered preterm birth solely due to placenta previa. Placental pathological lesions were assessed by a single placental pathologist, blinded to the group allocation, and described according to diagnostic criteria proposed by Redline et al in 2005. Statistics included Fisher’s exact test and Mann-Whitney U test. Results: Villous of fetal vascular thrombo-occlusive disease was found prominent in patients with FGR, regardless of PE (30.6% vs 0%, p¼0.012). Whereas, placental vascular lesions consistent with maternal
Abstracts / Placenta 36 (2015) A1eA60
protease with high expression during placental development in the mouse, rhesus monkey and human. In the human placenta, HtrA3 exists as long (HtrA3-L) and short (HtrA3-S) isoforms; they are identical except HtrA3-L has an extra C-terminal domain (the PDZ domain). Placental HtrA3 is secreted into the maternal circulation with its serum profile reflecting placental production. We have previously reported in a small cohort of samples that serum HtrA3 levels at the end of first trimester significantly differed between women who subsequently proceeded with normal pregnancy and who developed preeclampsia. In this study, using highly specific HtrA3 monoclonal antibodies that were generated in our laboratory, we established and fully validated ELISAs suitable for the detection of total HtrA3 and HtrA3-L in human serum. We then conducted a retrospective study to determine serum HtrA3 at 11e13 weeks of gestation in a cohort of singleton pregnancies that subsequently proceeded with normal pregnancy (control n ¼ 292), or were complicated with preeclampsia (n ¼ 41) or small for gestational age (SGA, n ¼ 71). Compared to controls, SGA pregnancies showed significantly lower levels of total HtrA3, with no difference in HtrA3-L. In contrast, HtrA3-L level was significantly higher in the preeclamptic cases compared to controls, with no difference in total HtrA3. In addition, early-onset preeclampsia, which occurs before 34 weeks of gestation, showed significantly lower ratio of HtrA3-L over total HtrA3 compared to the control group. These data support the potential utility of serum HtrA3 for the early detection of preeclampsia and SGA.
P2.53. A COMPARATIVE MORPHOMETRIC EVALUATION OF NORMOTENSIVE AND PRE-ECLAMPTIC PLACENTA FROM SOUTH AFRICAN PREGNANT WOMEN Kaminee Maduray, Jagidesa Moodley, Thajasvarie Naicker. University of KwaZulu-Natal, Durban, South Africa In sub-Saharan Africa, pre-eclampsia is one of the major direct causes of maternal mortality. The pathology of pre-eclampsia is not fully understood. However, delivery of the placenta resolves all clinical symptoms and signs. The placenta is therefore a vital organ in understanding the pathogenesis of pre-eclampsia. Objective: The aim of this study was to compare placentae morphometrics between normotensive and pre-eclamptic pregnancies. Methods: Placentae were collected from normotensive (n ¼ 30) and preeclamptic (n ¼ 30) pregnancies. At delivery, each placenta was photographed and analysed for variations in gross appearance, abnormalities, point of insertion of umbilical cord as well as thickness. The placental images were further analysed for placental volume and diameter with the Zeiss Axiovision Rel. 4.8 software. Results: Placentae of pre-eclamptic pregnancies showed more abnormalities with regards to shape and the presence of oedema compared to the normotensive group. Eccentric insertion of the umbilical cord was predominate in the normotensive (60%) compared to the pre-eclamptic (45%) group. Marginal insertion of the umbilical cord was found in 27% and 28% of the normotensive and pre-eclamptic group respectively; whilst central insertion was noted in 13% of the normotensive and 10% in the pre-eclamptic group. Velamentous insertion occurred in the preeclamptic (17%) but was absent in the normotensive pregnancies. The mean placental weight, thickness, diameter and volume in the normotensive group were 675 g, 1.6 cm, 27 cm and 1024 cm3 respectively; and those in the pre-eclamptic group were 577 g, 1.5 cm, 25 cm and 743 cm3 the respectively. Conclusion: This study concludes that the mean placental weight, thickness, diameter and volume were significantly lower in pre-eclampsia compared to normotensive pregnancies.
P2.54. DOWN-REGULATION OF PLACENTAL GLUCOSE TRANSPORTER (GLUT)-1 IN PRE-ECLAMPSIA Camilla Marini 2, 4, Xiao Messerli 1, 2,
Benjamin Huang 3, 4,
P.
€ rgerLüscher 1, 2, Marianne Jo Jürg Gertsch 3, Matthias A.
Hediger 3, Christiane Albrecht 3, Daniel V. Surbek 1,2, Marc U. Baumann 1, 2. 1 Department of Obstetrics and Gynecology, University Hospital of Bern, Bern, Switzerland; 2 Laboratory for Prenatal Medicine, Department of Clinical Research, University of Bern, Bern, Switzerland; 3 Institute for Biochemestry and Molecular Medicine, University of Bern, Bern, Switzerland; 4 Graduate School for Cellular and Biomedical Sciences (GCB), University of Bern, Bern, Switzerland Transplacental fetal glucose supply is predominantly regulated by glucose transporter-1 (GLUT1). Altered expression and/or function of GLUT1 may affect the intrauterine environment, which could compromise fetal development and could potentially lead to fetal programming. Until now it is unknown if placental GLUT1 is affected by pre-eclampsia (PE), a disease known to be associated with gestational diabetes (GDM) and IUGR. We therefore aimed to address the hypothesis that PE leads to altered expression and function of GLUT1. Placentae were obtained after elective caesarean sections following normal pregnancy and from pregnancies affected by PE. Syncytial basal membrane (BM) and apical microvillus membrane (MVM) fractions were prepared from syncytiotrophoblast (STB). GLUT1 protein expression was assessed by Western blot analysis and mRNA levels were quantified by qPCR. Radiolabeled glucose up-take assay, using placental-derived syncytial microvesicles and a transepithelial transport model using primary cytotrophoblasts were established to determine glucose transport activity. GLUT1 protein expression was significantly down-regulated in PE placentae compared to control placentae, while mRNA expression was unchanged. Glucose up-take into syncytial microvesicles was significantly reduced in PE compared to control. In a transepithelial transport model, phloretin-mediated inhibition of GLUT1 at the apical side of primary cytotrophoblast cells showed a significant shift of the transepithelial glucose transport. Our study shows for the first time that in PE, placental GLUT1 is downregulated on protein level and that GLUT1-mediated glucose transport activity is decreased. These suggest that GLUT1 might contribute to the pathogenetic link between PE and GDM, and eventually IUGR. Further, these data show that in PE GLUT1-mediated transplacental glucose transport is regulated on the apical side of the STB. Our results help to elucidate the role of GLUT1 in PE and to develop strategies to modulate glucose transport, aiming to reduce the risk for metabolic and cardiovascular diseases for the child later in life.
P2.55. PLACENTAL PATHOLOGIC FEATURES OF FETAL GROWTH RESTRICTION AND PREECLAMPSIA IN PRETERM: ARE PLACENTAL LESIONS DIFFERENT? Kylie Hae-Jin Chang, Ji-Hee Sung, Suk-Joo Choi, Soo-Young Oh, Jung-Sun Kim, Cheong-Rae Roh, Jong-Hwa Kim. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Objectives: Fetal growth restriction (FGR) and preeclampsia (PE) associate with increased neonatal morbidity, which occasionally accompany simultaneously. Altered normal placenta function and distorted structure is considered the most important pathological cause in both cases. This study aims to investigate the placental pathologic finding related to FGR and PE in preterm, by comparison. Methods: Preterm placenta (<35 weeks) from FGR (n ¼ 16), severe PE (n ¼ 16), both FGR and severe PE (n ¼ 20) and control pregnancies (n ¼ 30) were studied. Gestational age at delivery was equally matched between four groups. FGR was defined as fetal growth less than 5th percentile for gestational age and patients with chronic hypertension were excluded from the study population. Control group was composed of patients who delivered preterm birth solely due to placenta previa. Placental pathological lesions were assessed by a single placental pathologist, blinded to the group allocation, and described according to diagnostic criteria proposed by Redline et al in 2005. Statistics included Fisher’s exact test and Mann-Whitney U test. Results: Villous of fetal vascular thrombo-occlusive disease was found prominent in patients with FGR, regardless of PE (30.6% vs 0%, p¼0.012). Whereas, placental vascular lesions consistent with maternal