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Neuregulin-1beta1 is strongly expressed in the umbilical and villous endothelial cells in pregnancy induced hypertension
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Abstracts / Placenta 35 (2014) A1eA23
O-012. HDLIVE IMAGE OF INTRAUTERINE ABNORMALITIES Masato Mashima, Toshiyuki Hata, Hirokazu Tanaka, Kenji Kanenishi, Uiko Hanaoka, Nobuhiro Mori, Megumi Itou, Megumi Ishibashi, Tamaki Tanaka, Chiaki Tenkumo. Department of Perinatology and Gynecology, Kagawa University School of Medicine, Japan HDlive is a surface rendering mode that uses an adjustable light source adding to the conventional three-dimensional (3D) sonography. This light source can enhance 3D sonographic images in point of their depth, providing anatomically realistic appearances of the subjects. We present our experiences of a chorionic bump, a placental shelf and two uterine synechiae, and HDlive images of these intrauterine abnormalities. Case 1. A 28-year-old pregnant Japanese woman, gravida 1, para 0. At 7 weeks and 5 days of gestation, transvaginal sonography showed gestational sac which included embryo and yolk sac, but fetal heart movement was absent. We found out a cystic projection inside the gestational sac and made diagnosis of chorionic bump. The embryo and chorionic bump were clearly described with HDlive. Case 2. A 35-year-old pregnant Japanese woman, gravida 4, para 3, was referred to our clinic because of the suspicion of amniotic band syndrome. Two dimensional (2D) sonogoraphy depicted the placental shelf at the edge of the placenta. With using HDlive, three dimensional image of the placenta was described. Case 3. A 27-year-old pregnant Japanese woman, gravida 1, para 0. 2D sonography described oblique transverse uterine synechia at 26 weeks and 4days of gestation. The fetus was superior and the umbilical cord was blow the synechia. HDlive clearly showed the uterine synechia and umbilical cord prolapse. At 29weeks and 5 days of gestation, elective caesarean section was performed because of premature rapture of the membrane. Case 4. A 34-year-old pregnant Japanese woman, gravida 1, para 0, who had undergone at 21 age. At 28 weeks of gestation, 2D sonography and HDlive described a vertical bridging synechia between the anterior and posterior wall of the uterine. Elective caesarean section was performed because of malpresentation. Every four cases, HDlive provided realistic spatial features of the intrauterine abnormalities. HDlive may give the examiner additional information, comparing to 2D sonography.
O-017. ANGIOGENIC, CYTOPROTECTIVE, AND IMMUNOSUPPRESSIVE PROPERTIES OF HUMAN AMNION- AND CHORION-DERIVED MESENCHYMAL STEM CELLS Kenichi Yamahara a, Akihiko Taguchi b, Toshihiro Soma c, Hiroyasu Ogawa c, Tomoaki Ikeda d, Jun Yoshimatsu e. a Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Japan; b Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation, Japan; c Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Japan; d Department of Obstetrics & Gynecology, Mie University Faculty of Medicine, Japan; e Division of Maternal Fetal Medicine and Gynecology, National Cerebral and Cardiovascular Center, Japan Although mesenchymal stem cells (MSCs) can be obtained from the fetal membrane (FM), little information is available regarding biological differences in MSCs derived from different layers of the FM or their therapeutic potential. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced Tlymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of acute graft-
versus-host disease. Our results highlight that human amnion- and chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.
O-018. THREE CASES OF CHRONIC ABRUPTION-OLIGOHYDRAMNIOS SEQUENCE (CAOS). Rie Yoshida, Kazunori Mukaida, Hirotaka Nishi, Tomoyoshi Nohira, Keiichi Isaka. Department of Obstetrics and Gynecology,Tokyo Medical University, Japan Chronic abruption-oligohydramnios sequence (CAOS) reported by Elliott et al，is defined by clinically significant recurrent vaginal bleeding in the absence of placenta previa or other identifiable source of bleeding and oligohydramnios without concurrent evidence of ruptured membranes. It is associated with adverse pregnancy outcomes, including preterm delivery and pulmonary hypoplasia in the infant who should have a worse perinatal prognosis in comparison with other preterm infants born at similar gestational ages. We experienced three cases of CAOS. All cases had episodes of recurrent bleeding occurring in the first trimester of pregnancy. Two cases developed chronic lung disease (CLD) and resulted in neonatal death. The remaining case delivered at 22 weeks was stillbirth. Diffuse chorioamniotic hemosiderosis (DCA) which is suggestive of chronic bleeding, chorioamnionitis（CAM）and forcal infarction were observed in their placentas in two cases. Recently, it is described that there should be clinical association between DCA and CLD. The pathology of CAOS has been still unclear, whereas our observations indicate that patient with CAOS is a high-risk group for poor perinatal/neonatal outcomes. During the first trimester, recurrent and prolonged bleeding is an important sign of CAOS.
O-019. NEUREGULIN-1BETA1 IS STRONGLY EXPRESSED IN THE UMBILICAL AND VILLOUS ENDOTHELIAL CELLS IN PREGNANCY INDUCED HYPERTENSION Satoshi Ohira a, Ryoichi Asaka a, Hisanori Kobara a, Akiko Takatsu a, Norihiko Kikuchi a, Makoto Kanai b, Tanri Shiozawa a. a Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan; b Department of Family and Child Nursing, and Midwifery, Shinshu University School of Health Sciences, Japan Objectives: Neuregulin (NRG) -1 is a family of epidermal growth factor with a wide range of functions. Recently, NRG-1beta1 was reported to control fetal lung maturation through mesenchymal-epithelial interactions in a paracrine mechanism. To clarify the mechanism of paracrine regulation of NRG-1beta1 in the umbilical-placental system, we analyzed the expressions of NRG-1beta1 in the umbilical and villous endothelial cells in patients with pregnancy induced hypertension (PIH). Methods: Twenty-four placental tissues delivered between 22 and 34 weeks of gestation were obtained; 12 were with PIH, the remaining was control without PIH. Immunohistochemical expression of NRG-1beta1 in endothelium of blood vessels in the stem villi was examined. The result was scored according to the intensity of staining (no staining ¼ 0, weak staining ¼ 1, strong staining ¼ 2) in 10 blood vessels (Full score: 20). In hypoxic experiments, human umbilical vein endothelial cells (HUVEC) were cultured under various oxygen conditions (21%, 5% or 2% O2). Proteins extracted from cultures of HUVEC were subjected to a western blot analysis, using antibodies against NRG-1. Fifty-two umbilical venous bloods at delivery were obtained; 21 were with PIH, the remaining was control without PIH. The concentration of NRG-1 in the umbilical venous blood was measured using ELISA assay. Results: The mean NRG-1 immunostaining score for patients with PIH was 11.4.3, which was significantly increased compared with that in women without PIH (7.9±2.1; p<0.05). Western blotting revealed that the expression of NRG-1beta1was increased in a lower oxygen concentration in HUVEC. The mean plasma NRG-1beta1 levels in the umbilical venous
Abstracts / Placenta 35 (2014) A1eA23
blood in PIH patients was 2.18 ± 1.30 ng/mL, and was significantly higher than that of control patients (1.33±0.73ng/mL; p<0.05). Conclusion: The elevated expression of NRG-1beta1 in the umbilical and villous endothelial cells in patients with PIH may stimulate fetal lung maturation.
O-020. INVOLVEMENT OF VISCERAL ADIPOSE TISSUE IN MODULATION OF INFLAMMATORY CASCADE IN PREECLAMPSIA Juria Akasaka, Katsuhiko Naruse, Natsuki Koike, Taihei Tsunemi, Hiroshi Shigetomi, Chiharu Yoshimoto, Hiroshi Kobayashi. Nara Medical University Department of Obstetrics and Gynecology, Japan Objectives: The pathophysiology of preeclampsia is characterized by abnormal placentation, dysfunction of the maternal endothelium and an exaggerated inflammatory response. Recently it is considered that the adipose tissue is a key organ for highly active immune response, endocrine and metabolism. In this study, we established new method for bottom culture of adipose tissue containing not only adipocyte but other cells and connective tissue, and investigated the effects of preeclampsia serum on the expression of inflammation-related genes by the tissue. Methods: Visceral adipose tissue was obtained from the omentum of patients with early ovarian cancer without metastasis. Dissected visceral fat was captured on the bottom of the 24 well plastic plate with 99.5% medium-containing hydrogel (PuraMatrix, Becton Dickinson & Co.) Adipose tissue was incubated either with 10% serum obtained from five women with severe preeclampsia or five normal pregnant women. 370 genes in total mRNA were analyzed with quantitative RT-PCR array (Inflammatory Response & Autoimmunity gene set, RT2 Profiler PCR Array, Qiagen Inc., Germany). Results: Gene expression analysis revealed changes in the expression levels of 30 genes in adipose tissue treated with preeclampsia serum. Some genes altered are related to immune response, oxidative stress, insulin resistance and adipogenesis, which play a central role in excessive systemic inflammatory response of preeclampsia. In contrast, other genes suppressing inflammation through upregulation of Th2 cytokine predominance, anti-oxidative stress and insulin sensitivity were also increased. Conclusion: In our study, addition of preeclampsia serum including placental danger signal on adipose tissue not only induced inflammatory activities but also suppressed. Visceral adipose tissue might have protective role against inflammation, oxidative insults and other forms of cellular stress that are the key of the pathogenesis of preeclampsia.
O-021. THREE-DIMENSIONAL ULTRASOUND EVALUATION OF TWO CASES OF UMBILICAL VEIN VARIX Kenji Kanenishi, Emiko Nitta, Masato Mashima, Tamaki Tanaka, Megumi Ishibashi, Megumi Ito, Nobuhiro Mori, Uiko Hanaoka, Hirokazu Tanaka, Toshiyuki Hata. Department of Perinatology and Gynecology, Kagawa University School of Medicine, Japan Umbilical cord varix exhibits a marked dilatation of the umbilical vein, and intrinsic weakness of the umbilical vein wall may be the underling etiology of venous dilatation and development of the varix. There are two types of umbilica vein varix (UVV): varix formed in the fetal abdomen (intraabdominal) and in the amniotic fluid (intra-amniotic). In this report, we present a case of intra-amniotic and a case of inta-abdominal UVV diagnosed with conventional two-dimentional (2D) sonography, power Doppler ultrasound, three-dimentional (3D) HD-flow and HDlive. Case report: intra-amniotic UVV case; 34-year-old women, gravida 2, para 1, was referred to our ultrasonography clinic because of a suspected umbilical cord abnormality at 35 weeks of gestation. Showed a large thrombus in the umbilical cord, which is an extension including varix a maximum diameter of 25.5mm in 2D ultrasound findings. Power Doppler and 3DHD-
A9
flow revealed bidirectional turbulent flow inside varix. Elective caesarean section was performed at 35 weeks pregnant. A male infant weighing 2501 g was delivered. The macroscopic and microscopic findings revealed umbilical cord vein varix with thrombosis. intra-abdominal UVV case; 30year-old women, gravida 1, para 0, was referred to our ultrasound clinic at 20 weeks due to sonographic finding of bilateral choroid plexus cysts. And a dilatation of the intra-abdominal portion of the umbilical vein (11.5mm) was identified between the fetal abdominal wall and inferior edge of the liver at 27 weeks. 3D/4D color/power doppler clarified the entire varix and affected vein’s shape and contour. Abnormal findings, such as thrombus was not observed, varix was confirmed that it was a normal size regressed in the course followed by observation.
O-023. IMMUNE ACTIVATION CAUSES PREECLAMPSIA-LIKE SYMPTOMS THROUGH THE CD40-CD40 LIGAND PATHWAY IN PREGNANT MICE Yuka Uchikura, Keiichi Matsubara, Yuko Matsubara, Miki Mori, Akihiro Nawa. Department of Obstetrics and Gynecology, Ehime University School of Medicine, Japan We created a PE mouse (ICR) model to illustrate impaired implantation by immune system activation just after implantation, a critical step in the pathogenesis of PE. This new model enabled the study of placentation. Using this mouse model, we were able to demonstrate the occurrence of some phenotypes of PE, including elevated systolic blood pressure, proteinuria, and decreased neonatal birth weight. Histopathological analyses revealed placental and renal changes in mice that are consistent with PE in humans. With this new model, we also documented increased production of interferon-g by helper T cells. On the other hand, Treg, which is in the normal placenta, was not found in the PE placenta. These results indicated that CD40L-induced helper T cell type 1 differentiation plays a critical role in the pathogenesis of PE through immune system activation. We believe that this new model will enable future research of the primary pathogenesis of PE and immune system modulation during pregnancy.
O-025. SIGNIFICANCE OF ABNORMAL CORD INSERTION FOR PERINATAL OUTCOME IN MONOCHORIONIC TWIN PREGNANCIES Keisuke Ishii a, Hiroshi Kawamura a, Aki Naoto Yonetani a, a a Shusaku Hayashi , Makoto Takeuchi b, Nobuaki Mabuchi , Mitsuda a. a Department of Maternal Fetal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan; b Department of Pathology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan Objective: To evaluate the association between abnormal cord insertion (ACI) and perinatal adverse outcomes, including twin-twin transfusion syndrome (TTTS), in monochorionic twin pregnancies in cases managed from the first trimester onward at a single center. Methods: All monochorionic diamniotic twin pregnancies, which received prenatal care before 16 weeks of gestation and delivered at our center between 2004 and 2013, were included in this retrospective cohort study. Macroscopically-defined ACI included velamentous cord insertion (VCI) and marginal cord insertion. The effects of ACI on TTTS and a composite of adverse outcomes, including death and neurological morbidities at 28 days after birth, were evaluated with a multiple logistic regression model. Results: A total of 357monochorionic diamniotic twin pregnancies were analyzed. ACI in at least one twin was noted in 64.9% of cases. VCI in both twins was noted in 2.5% of cases and VCI was noted in one twin in 22.1% of cases. The incidence of TTTS was 8.4%; the incidence of a composite of adverse outcomes in at least one twin was 9.8%. There was no correlation between ACI and TTTS as well as between ACI and a composite of adverse outcomes. Only VCI in both twins had a significant risk for death of both twins (adjusted odds ratio: 8.37; 95% confidence interval: 1.02-48.93; P ¼ 0.04). Conclusions: ACI in monochorionic twin pregnancies was not a risk factor for TTTS, while VCI in both twins was associated with perinatal death.
Abstracts / Placenta 35 (2014) A1eA23
O-012. HDLIVE IMAGE OF INTRAUTERINE ABNORMALITIES Masato Mashima, Toshiyuki Hata, Hirokazu Tanaka, Kenji Kanenishi, Uiko Hanaoka, Nobuhiro Mori, Megumi Itou, Megumi Ishibashi, Tamaki Tanaka, Chiaki Tenkumo. Department of Perinatology and Gynecology, Kagawa University School of Medicine, Japan HDlive is a surface rendering mode that uses an adjustable light source adding to the conventional three-dimensional (3D) sonography. This light source can enhance 3D sonographic images in point of their depth, providing anatomically realistic appearances of the subjects. We present our experiences of a chorionic bump, a placental shelf and two uterine synechiae, and HDlive images of these intrauterine abnormalities. Case 1. A 28-year-old pregnant Japanese woman, gravida 1, para 0. At 7 weeks and 5 days of gestation, transvaginal sonography showed gestational sac which included embryo and yolk sac, but fetal heart movement was absent. We found out a cystic projection inside the gestational sac and made diagnosis of chorionic bump. The embryo and chorionic bump were clearly described with HDlive. Case 2. A 35-year-old pregnant Japanese woman, gravida 4, para 3, was referred to our clinic because of the suspicion of amniotic band syndrome. Two dimensional (2D) sonogoraphy depicted the placental shelf at the edge of the placenta. With using HDlive, three dimensional image of the placenta was described. Case 3. A 27-year-old pregnant Japanese woman, gravida 1, para 0. 2D sonography described oblique transverse uterine synechia at 26 weeks and 4days of gestation. The fetus was superior and the umbilical cord was blow the synechia. HDlive clearly showed the uterine synechia and umbilical cord prolapse. At 29weeks and 5 days of gestation, elective caesarean section was performed because of premature rapture of the membrane. Case 4. A 34-year-old pregnant Japanese woman, gravida 1, para 0, who had undergone at 21 age. At 28 weeks of gestation, 2D sonography and HDlive described a vertical bridging synechia between the anterior and posterior wall of the uterine. Elective caesarean section was performed because of malpresentation. Every four cases, HDlive provided realistic spatial features of the intrauterine abnormalities. HDlive may give the examiner additional information, comparing to 2D sonography.
O-017. ANGIOGENIC, CYTOPROTECTIVE, AND IMMUNOSUPPRESSIVE PROPERTIES OF HUMAN AMNION- AND CHORION-DERIVED MESENCHYMAL STEM CELLS Kenichi Yamahara a, Akihiko Taguchi b, Toshihiro Soma c, Hiroyasu Ogawa c, Tomoaki Ikeda d, Jun Yoshimatsu e. a Department of Regenerative Medicine, National Cerebral and Cardiovascular Center, Japan; b Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation, Japan; c Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Japan; d Department of Obstetrics & Gynecology, Mie University Faculty of Medicine, Japan; e Division of Maternal Fetal Medicine and Gynecology, National Cerebral and Cardiovascular Center, Japan Although mesenchymal stem cells (MSCs) can be obtained from the fetal membrane (FM), little information is available regarding biological differences in MSCs derived from different layers of the FM or their therapeutic potential. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced Tlymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of acute graft-
versus-host disease. Our results highlight that human amnion- and chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.
O-018. THREE CASES OF CHRONIC ABRUPTION-OLIGOHYDRAMNIOS SEQUENCE (CAOS). Rie Yoshida, Kazunori Mukaida, Hirotaka Nishi, Tomoyoshi Nohira, Keiichi Isaka. Department of Obstetrics and Gynecology,Tokyo Medical University, Japan Chronic abruption-oligohydramnios sequence (CAOS) reported by Elliott et al，is defined by clinically significant recurrent vaginal bleeding in the absence of placenta previa or other identifiable source of bleeding and oligohydramnios without concurrent evidence of ruptured membranes. It is associated with adverse pregnancy outcomes, including preterm delivery and pulmonary hypoplasia in the infant who should have a worse perinatal prognosis in comparison with other preterm infants born at similar gestational ages. We experienced three cases of CAOS. All cases had episodes of recurrent bleeding occurring in the first trimester of pregnancy. Two cases developed chronic lung disease (CLD) and resulted in neonatal death. The remaining case delivered at 22 weeks was stillbirth. Diffuse chorioamniotic hemosiderosis (DCA) which is suggestive of chronic bleeding, chorioamnionitis（CAM）and forcal infarction were observed in their placentas in two cases. Recently, it is described that there should be clinical association between DCA and CLD. The pathology of CAOS has been still unclear, whereas our observations indicate that patient with CAOS is a high-risk group for poor perinatal/neonatal outcomes. During the first trimester, recurrent and prolonged bleeding is an important sign of CAOS.
O-019. NEUREGULIN-1BETA1 IS STRONGLY EXPRESSED IN THE UMBILICAL AND VILLOUS ENDOTHELIAL CELLS IN PREGNANCY INDUCED HYPERTENSION Satoshi Ohira a, Ryoichi Asaka a, Hisanori Kobara a, Akiko Takatsu a, Norihiko Kikuchi a, Makoto Kanai b, Tanri Shiozawa a. a Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Japan; b Department of Family and Child Nursing, and Midwifery, Shinshu University School of Health Sciences, Japan Objectives: Neuregulin (NRG) -1 is a family of epidermal growth factor with a wide range of functions. Recently, NRG-1beta1 was reported to control fetal lung maturation through mesenchymal-epithelial interactions in a paracrine mechanism. To clarify the mechanism of paracrine regulation of NRG-1beta1 in the umbilical-placental system, we analyzed the expressions of NRG-1beta1 in the umbilical and villous endothelial cells in patients with pregnancy induced hypertension (PIH). Methods: Twenty-four placental tissues delivered between 22 and 34 weeks of gestation were obtained; 12 were with PIH, the remaining was control without PIH. Immunohistochemical expression of NRG-1beta1 in endothelium of blood vessels in the stem villi was examined. The result was scored according to the intensity of staining (no staining ¼ 0, weak staining ¼ 1, strong staining ¼ 2) in 10 blood vessels (Full score: 20). In hypoxic experiments, human umbilical vein endothelial cells (HUVEC) were cultured under various oxygen conditions (21%, 5% or 2% O2). Proteins extracted from cultures of HUVEC were subjected to a western blot analysis, using antibodies against NRG-1. Fifty-two umbilical venous bloods at delivery were obtained; 21 were with PIH, the remaining was control without PIH. The concentration of NRG-1 in the umbilical venous blood was measured using ELISA assay. Results: The mean NRG-1 immunostaining score for patients with PIH was 11.4.3, which was significantly increased compared with that in women without PIH (7.9±2.1; p<0.05). Western blotting revealed that the expression of NRG-1beta1was increased in a lower oxygen concentration in HUVEC. The mean plasma NRG-1beta1 levels in the umbilical venous
Abstracts / Placenta 35 (2014) A1eA23
blood in PIH patients was 2.18 ± 1.30 ng/mL, and was significantly higher than that of control patients (1.33±0.73ng/mL; p<0.05). Conclusion: The elevated expression of NRG-1beta1 in the umbilical and villous endothelial cells in patients with PIH may stimulate fetal lung maturation.
O-020. INVOLVEMENT OF VISCERAL ADIPOSE TISSUE IN MODULATION OF INFLAMMATORY CASCADE IN PREECLAMPSIA Juria Akasaka, Katsuhiko Naruse, Natsuki Koike, Taihei Tsunemi, Hiroshi Shigetomi, Chiharu Yoshimoto, Hiroshi Kobayashi. Nara Medical University Department of Obstetrics and Gynecology, Japan Objectives: The pathophysiology of preeclampsia is characterized by abnormal placentation, dysfunction of the maternal endothelium and an exaggerated inflammatory response. Recently it is considered that the adipose tissue is a key organ for highly active immune response, endocrine and metabolism. In this study, we established new method for bottom culture of adipose tissue containing not only adipocyte but other cells and connective tissue, and investigated the effects of preeclampsia serum on the expression of inflammation-related genes by the tissue. Methods: Visceral adipose tissue was obtained from the omentum of patients with early ovarian cancer without metastasis. Dissected visceral fat was captured on the bottom of the 24 well plastic plate with 99.5% medium-containing hydrogel (PuraMatrix, Becton Dickinson & Co.) Adipose tissue was incubated either with 10% serum obtained from five women with severe preeclampsia or five normal pregnant women. 370 genes in total mRNA were analyzed with quantitative RT-PCR array (Inflammatory Response & Autoimmunity gene set, RT2 Profiler PCR Array, Qiagen Inc., Germany). Results: Gene expression analysis revealed changes in the expression levels of 30 genes in adipose tissue treated with preeclampsia serum. Some genes altered are related to immune response, oxidative stress, insulin resistance and adipogenesis, which play a central role in excessive systemic inflammatory response of preeclampsia. In contrast, other genes suppressing inflammation through upregulation of Th2 cytokine predominance, anti-oxidative stress and insulin sensitivity were also increased. Conclusion: In our study, addition of preeclampsia serum including placental danger signal on adipose tissue not only induced inflammatory activities but also suppressed. Visceral adipose tissue might have protective role against inflammation, oxidative insults and other forms of cellular stress that are the key of the pathogenesis of preeclampsia.
O-021. THREE-DIMENSIONAL ULTRASOUND EVALUATION OF TWO CASES OF UMBILICAL VEIN VARIX Kenji Kanenishi, Emiko Nitta, Masato Mashima, Tamaki Tanaka, Megumi Ishibashi, Megumi Ito, Nobuhiro Mori, Uiko Hanaoka, Hirokazu Tanaka, Toshiyuki Hata. Department of Perinatology and Gynecology, Kagawa University School of Medicine, Japan Umbilical cord varix exhibits a marked dilatation of the umbilical vein, and intrinsic weakness of the umbilical vein wall may be the underling etiology of venous dilatation and development of the varix. There are two types of umbilica vein varix (UVV): varix formed in the fetal abdomen (intraabdominal) and in the amniotic fluid (intra-amniotic). In this report, we present a case of intra-amniotic and a case of inta-abdominal UVV diagnosed with conventional two-dimentional (2D) sonography, power Doppler ultrasound, three-dimentional (3D) HD-flow and HDlive. Case report: intra-amniotic UVV case; 34-year-old women, gravida 2, para 1, was referred to our ultrasonography clinic because of a suspected umbilical cord abnormality at 35 weeks of gestation. Showed a large thrombus in the umbilical cord, which is an extension including varix a maximum diameter of 25.5mm in 2D ultrasound findings. Power Doppler and 3DHD-
A9
flow revealed bidirectional turbulent flow inside varix. Elective caesarean section was performed at 35 weeks pregnant. A male infant weighing 2501 g was delivered. The macroscopic and microscopic findings revealed umbilical cord vein varix with thrombosis. intra-abdominal UVV case; 30year-old women, gravida 1, para 0, was referred to our ultrasound clinic at 20 weeks due to sonographic finding of bilateral choroid plexus cysts. And a dilatation of the intra-abdominal portion of the umbilical vein (11.5mm) was identified between the fetal abdominal wall and inferior edge of the liver at 27 weeks. 3D/4D color/power doppler clarified the entire varix and affected vein’s shape and contour. Abnormal findings, such as thrombus was not observed, varix was confirmed that it was a normal size regressed in the course followed by observation.
O-023. IMMUNE ACTIVATION CAUSES PREECLAMPSIA-LIKE SYMPTOMS THROUGH THE CD40-CD40 LIGAND PATHWAY IN PREGNANT MICE Yuka Uchikura, Keiichi Matsubara, Yuko Matsubara, Miki Mori, Akihiro Nawa. Department of Obstetrics and Gynecology, Ehime University School of Medicine, Japan We created a PE mouse (ICR) model to illustrate impaired implantation by immune system activation just after implantation, a critical step in the pathogenesis of PE. This new model enabled the study of placentation. Using this mouse model, we were able to demonstrate the occurrence of some phenotypes of PE, including elevated systolic blood pressure, proteinuria, and decreased neonatal birth weight. Histopathological analyses revealed placental and renal changes in mice that are consistent with PE in humans. With this new model, we also documented increased production of interferon-g by helper T cells. On the other hand, Treg, which is in the normal placenta, was not found in the PE placenta. These results indicated that CD40L-induced helper T cell type 1 differentiation plays a critical role in the pathogenesis of PE through immune system activation. We believe that this new model will enable future research of the primary pathogenesis of PE and immune system modulation during pregnancy.
O-025. SIGNIFICANCE OF ABNORMAL CORD INSERTION FOR PERINATAL OUTCOME IN MONOCHORIONIC TWIN PREGNANCIES Keisuke Ishii a, Hiroshi Kawamura a, Aki Naoto Yonetani a, a a Shusaku Hayashi , Makoto Takeuchi b, Nobuaki Mabuchi , Mitsuda a. a Department of Maternal Fetal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan; b Department of Pathology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan Objective: To evaluate the association between abnormal cord insertion (ACI) and perinatal adverse outcomes, including twin-twin transfusion syndrome (TTTS), in monochorionic twin pregnancies in cases managed from the first trimester onward at a single center. Methods: All monochorionic diamniotic twin pregnancies, which received prenatal care before 16 weeks of gestation and delivered at our center between 2004 and 2013, were included in this retrospective cohort study. Macroscopically-defined ACI included velamentous cord insertion (VCI) and marginal cord insertion. The effects of ACI on TTTS and a composite of adverse outcomes, including death and neurological morbidities at 28 days after birth, were evaluated with a multiple logistic regression model. Results: A total of 357monochorionic diamniotic twin pregnancies were analyzed. ACI in at least one twin was noted in 64.9% of cases. VCI in both twins was noted in 2.5% of cases and VCI was noted in one twin in 22.1% of cases. The incidence of TTTS was 8.4%; the incidence of a composite of adverse outcomes in at least one twin was 9.8%. There was no correlation between ACI and TTTS as well as between ACI and a composite of adverse outcomes. Only VCI in both twins had a significant risk for death of both twins (adjusted odds ratio: 8.37; 95% confidence interval: 1.02-48.93; P ¼ 0.04). Conclusions: ACI in monochorionic twin pregnancies was not a risk factor for TTTS, while VCI in both twins was associated with perinatal death.