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The relationship of inflammatory changes and fetal prognosis of the placenta in histological chorioamnionitis
Abstracts / Placenta 46 (2016) 102e121
103
EFFICACY OF CEUS IN THE PREDICTION OF EXCESSIVE HEMORRHAGE AFTER CS WITH ABNORMAL PLACENTATION
THE EXPRESSION AND ROLE OF CD59 IN HUMAN EXTRAVILLOUS TROPHOBLAST
Kenji Imai, Tomomi Kotani, Yumiko Ito, Shima Hirako, Tomoko Nakano, Hiroyuki Tsuda, Fumitaka Kikkawa. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Japan
Masashi Ueda 1, Akihito Horie 1, Yukiyasu Sato 2, Hirohiko Tani 1, Yumiko Miyazaki 1, Asuka Okunomiya 1, Matsumura Noriomi 1. 1 Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan; 2 Department of Obstetrics and Gynecology, Otsu Red Cross Hospital, Japan
Background: Post-partum hemorrhage (PPH) remains the leading cause of maternal mortality worldwide. Abnormal Placentation, especially placenta previa and low-lying placenta is a major risk factor of PPH not only during surgery but also in postoperative period, and early detection and/or prediction in these conditions can more readily enable the physician to minimize the risks to mother and fetus. The purpose of this study is to evaluate the possibility of CEUS for novel management of abnormal placentation. Methods: This study was approved by Ethics Committee of our institute and performed retrospectively. Between October 2015 and June 2016, 10 patients, including six cases of placenta previa and four cases of low-lying placenta, were underwent CEUS after elective CS and enrolled in this study. CEUS was performed by at least two obstetricians, and was classified as positive when pooling of leaked contrast agent was observed in the uterine lumen. Hemorrhage after CS was defined as blood loss during the first 4 hours after operation. Results: Mean pregnant weeks; 36w (range 31-38w), mean birth weight; 2767g (1950-3076g), mean operative time; 65.9min (49-108min), mean shock index before CEUS; 0.66 (0.47-0.89). The mean blood loss of nine patients which classified negative CEUS was 37.3mL (4-78mL). By contrast, one patient which classified positive CEUS had large amount of hemorrhage (141mL). No side effects were found in this study. Conclusion: In the patients with placenta previa or low-lying placenta, CEUS might be effective for prediction of excessive hemorrhage after CS.
THE RELATIONSHIP OF INFLAMMATORY CHANGES AND FETAL PROGNOSIS OF THE PLACENTA IN HISTOLOGICAL CHORIOAMNIONITIS Chiharu Tomonaga 1, Eiji Shibata 1, Satoshi Aramaki 2, Yukiyo Aiko 2, Hirohide Inagaki 1, Toru Hachisuga 1. 1 Department of Obstetrics and Gynecology, University of Occupational and Environmental Health, Japan; 2 Maternal and Fetal Intensive Care Unit, University of Occupational and Environmental Health, Japan Object: We investigated to the prognosis and placental damage of pregnant women complicated by histological chorioamnionitis (HCA) in full term delivery. Methods: 30 cases of HCA group and 10 cases of non-HCA control were chosen for examination. HCA group was divided by CAM stagesⅠ(n:10),Ⅱ(n:10) and Ⅲ(n:10). We analyzed maternal and neonatal outcomes, and placental oxidative stress, cytokine signal and immuno response by immunohistological detection. Oxidative stress exhausted by Hsp27, 4HNE- modified proteins, cytokine signal was exhausted by SOCS3. Activation of immune system was exhausted by CD64 expression. Results: HCA group had a significant increase in the ratio of the duration of 1st labor stage compared with non- HCA group. CAM stageⅡand Ⅲ was showed to increase in the ratio of period of PROM compared with CAM stageⅠ. But there was not significant differences in neonatal birth condition and infection between HCA and non-HCA group. In immunohistochemical analysis in placenta, Hsp27, 4HNE and SOCS-3 was expressed at cytoplasma and nucleuses of syncytiotrophoblast strongly. CD64 was located in shown at white blood cells of the intervillous space and Hofbauer cell in the villus. Signal intensity of those proteins in placenta was not found to be different between HCA and nonHCA group. Conclusion: HCA of full term delivery do not affect with neonatal outcomes and placental oxidative stress, cytokine signal and immune system.
Objective: In human placenta, extravillous trophoblast (EVT) invades maternal decidua and the spiral artery (endovascular EVT, eEVT). Although eEVT makes direct contact with complement components contained in the maternal blood, eEVT is not eliminated by their activation. We focused on CD59 which is an 18-20 kDa glycosylphosphatidylinositol- anchored protein. CD59 inhibits the formation of membrane attack complex (MAC), a final product in the complement activation. In this study, we investigated the expression and the function of CD59 in EVT. Method: Samples of early implantation sites were obtained from the hysterectomy during pregnancy and were subjected to immunohistochemistry using anti-CD59 antibody. The first-trimester chorionic tissues were obtained from artificial abortions and were subjected to the primary organ cultures to isolate EVT (isolated EVT cells). Isolated EVT cells were cultured in hypoxic conditions and change in CD59 expression level was examined by immunocytochemistry. Use of these samples was approved by the Ethics Committee of Kyoto University Hospital. Human immortalized EVT cell line (Swan71) and CD59-silenced Swan71 (Sw/CD59-sh), which was established by shRNA knockdown approach, were compared using WST assay, invasion assay and apoptosis assay. Results: In immunohistochemistry, CD59 expression was higher on eEVT and syncytiotrophoblast than on other trophoblast lineages. In immunocytochemistry, CD59 expression on isolated EVT was decreased in hypoxic conditions. Although no significant difference in cell proliferation or invasion was observed between control Swan71 and Sw/CD59-sh, cell apoptosis induced by treatment with complement components was significantly more exaggerated in Sw/CD59-sh than in control Swan 71. Conclusions: CD59 may play a crucial role in protection of eEVT against maternal complement system.
THE ROLE OF EPAC2/RAP1-MEDIATED TROPHOBLAST DIFFERENTIATION
CAMP
SIGNALING
IN
Mikihiro Yoshie 1, Kazuhiro Tamura 1, Gen Ishikawa 2, Takako Ohmaru 3, Misaki Okada 1, Rinna Tamakoshi 1, Akihito Nakai 2, Toshiyuki Takeshita 2, Kiyoko Kato 3, Hirotaka Nishi 4, Keiichi Isaka 4, Naoko Kuwabara 1, Eiichi Tachikawa 1. 1 Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, Japan; 2 Department of Obstetrics and Gynecology, Nippon Medical School, Japan; 3 Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Japan; 4 Department of Obstetrics and Gynecology, Tokyo Medical University, Japan Objective: Differentiation of cytotrophoblasts into syncytiotrophoblasts is essential for maintenance of villous function and fetal development during pregnancy. In this study, we examine the role of Exchange protein directly activated by cAMP 2 (EPAC2), a mediator of cAMP signaling pathway in the production of chorionic gonadotropin (HCG) and progesterone (P4) and the expression of cell fusion- associated factors in human trophoblast cells. Methods: Trophoblast cells isolated from the chorionic villi of the human term placenta were pretreated with ESI-05, an inhibitor of EPAC2 for 1 h, and then incubated with dibutyrylcAMP (db-cAMP) for 48 h. The expression of both a and b subunits of HCG, cholesterol side-chain cleavage enzyme (P450scc), syncytins 1 and 2 was analyzed by real-time RT- PCR. The level of HCG and P4 in the culture media was determined by immunoblotting and ELISA, respectively. Changes in EPAC2-mediated signaling
103
EFFICACY OF CEUS IN THE PREDICTION OF EXCESSIVE HEMORRHAGE AFTER CS WITH ABNORMAL PLACENTATION
THE EXPRESSION AND ROLE OF CD59 IN HUMAN EXTRAVILLOUS TROPHOBLAST
Kenji Imai, Tomomi Kotani, Yumiko Ito, Shima Hirako, Tomoko Nakano, Hiroyuki Tsuda, Fumitaka Kikkawa. Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Japan
Masashi Ueda 1, Akihito Horie 1, Yukiyasu Sato 2, Hirohiko Tani 1, Yumiko Miyazaki 1, Asuka Okunomiya 1, Matsumura Noriomi 1. 1 Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan; 2 Department of Obstetrics and Gynecology, Otsu Red Cross Hospital, Japan
Background: Post-partum hemorrhage (PPH) remains the leading cause of maternal mortality worldwide. Abnormal Placentation, especially placenta previa and low-lying placenta is a major risk factor of PPH not only during surgery but also in postoperative period, and early detection and/or prediction in these conditions can more readily enable the physician to minimize the risks to mother and fetus. The purpose of this study is to evaluate the possibility of CEUS for novel management of abnormal placentation. Methods: This study was approved by Ethics Committee of our institute and performed retrospectively. Between October 2015 and June 2016, 10 patients, including six cases of placenta previa and four cases of low-lying placenta, were underwent CEUS after elective CS and enrolled in this study. CEUS was performed by at least two obstetricians, and was classified as positive when pooling of leaked contrast agent was observed in the uterine lumen. Hemorrhage after CS was defined as blood loss during the first 4 hours after operation. Results: Mean pregnant weeks; 36w (range 31-38w), mean birth weight; 2767g (1950-3076g), mean operative time; 65.9min (49-108min), mean shock index before CEUS; 0.66 (0.47-0.89). The mean blood loss of nine patients which classified negative CEUS was 37.3mL (4-78mL). By contrast, one patient which classified positive CEUS had large amount of hemorrhage (141mL). No side effects were found in this study. Conclusion: In the patients with placenta previa or low-lying placenta, CEUS might be effective for prediction of excessive hemorrhage after CS.
THE RELATIONSHIP OF INFLAMMATORY CHANGES AND FETAL PROGNOSIS OF THE PLACENTA IN HISTOLOGICAL CHORIOAMNIONITIS Chiharu Tomonaga 1, Eiji Shibata 1, Satoshi Aramaki 2, Yukiyo Aiko 2, Hirohide Inagaki 1, Toru Hachisuga 1. 1 Department of Obstetrics and Gynecology, University of Occupational and Environmental Health, Japan; 2 Maternal and Fetal Intensive Care Unit, University of Occupational and Environmental Health, Japan Object: We investigated to the prognosis and placental damage of pregnant women complicated by histological chorioamnionitis (HCA) in full term delivery. Methods: 30 cases of HCA group and 10 cases of non-HCA control were chosen for examination. HCA group was divided by CAM stagesⅠ(n:10),Ⅱ(n:10) and Ⅲ(n:10). We analyzed maternal and neonatal outcomes, and placental oxidative stress, cytokine signal and immuno response by immunohistological detection. Oxidative stress exhausted by Hsp27, 4HNE- modified proteins, cytokine signal was exhausted by SOCS3. Activation of immune system was exhausted by CD64 expression. Results: HCA group had a significant increase in the ratio of the duration of 1st labor stage compared with non- HCA group. CAM stageⅡand Ⅲ was showed to increase in the ratio of period of PROM compared with CAM stageⅠ. But there was not significant differences in neonatal birth condition and infection between HCA and non-HCA group. In immunohistochemical analysis in placenta, Hsp27, 4HNE and SOCS-3 was expressed at cytoplasma and nucleuses of syncytiotrophoblast strongly. CD64 was located in shown at white blood cells of the intervillous space and Hofbauer cell in the villus. Signal intensity of those proteins in placenta was not found to be different between HCA and nonHCA group. Conclusion: HCA of full term delivery do not affect with neonatal outcomes and placental oxidative stress, cytokine signal and immune system.
Objective: In human placenta, extravillous trophoblast (EVT) invades maternal decidua and the spiral artery (endovascular EVT, eEVT). Although eEVT makes direct contact with complement components contained in the maternal blood, eEVT is not eliminated by their activation. We focused on CD59 which is an 18-20 kDa glycosylphosphatidylinositol- anchored protein. CD59 inhibits the formation of membrane attack complex (MAC), a final product in the complement activation. In this study, we investigated the expression and the function of CD59 in EVT. Method: Samples of early implantation sites were obtained from the hysterectomy during pregnancy and were subjected to immunohistochemistry using anti-CD59 antibody. The first-trimester chorionic tissues were obtained from artificial abortions and were subjected to the primary organ cultures to isolate EVT (isolated EVT cells). Isolated EVT cells were cultured in hypoxic conditions and change in CD59 expression level was examined by immunocytochemistry. Use of these samples was approved by the Ethics Committee of Kyoto University Hospital. Human immortalized EVT cell line (Swan71) and CD59-silenced Swan71 (Sw/CD59-sh), which was established by shRNA knockdown approach, were compared using WST assay, invasion assay and apoptosis assay. Results: In immunohistochemistry, CD59 expression was higher on eEVT and syncytiotrophoblast than on other trophoblast lineages. In immunocytochemistry, CD59 expression on isolated EVT was decreased in hypoxic conditions. Although no significant difference in cell proliferation or invasion was observed between control Swan71 and Sw/CD59-sh, cell apoptosis induced by treatment with complement components was significantly more exaggerated in Sw/CD59-sh than in control Swan 71. Conclusions: CD59 may play a crucial role in protection of eEVT against maternal complement system.
THE ROLE OF EPAC2/RAP1-MEDIATED TROPHOBLAST DIFFERENTIATION
CAMP
SIGNALING
IN
Mikihiro Yoshie 1, Kazuhiro Tamura 1, Gen Ishikawa 2, Takako Ohmaru 3, Misaki Okada 1, Rinna Tamakoshi 1, Akihito Nakai 2, Toshiyuki Takeshita 2, Kiyoko Kato 3, Hirotaka Nishi 4, Keiichi Isaka 4, Naoko Kuwabara 1, Eiichi Tachikawa 1. 1 Department of Endocrine and Neural Pharmacology, Tokyo University of Pharmacy and Life Sciences, Japan; 2 Department of Obstetrics and Gynecology, Nippon Medical School, Japan; 3 Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Japan; 4 Department of Obstetrics and Gynecology, Tokyo Medical University, Japan Objective: Differentiation of cytotrophoblasts into syncytiotrophoblasts is essential for maintenance of villous function and fetal development during pregnancy. In this study, we examine the role of Exchange protein directly activated by cAMP 2 (EPAC2), a mediator of cAMP signaling pathway in the production of chorionic gonadotropin (HCG) and progesterone (P4) and the expression of cell fusion- associated factors in human trophoblast cells. Methods: Trophoblast cells isolated from the chorionic villi of the human term placenta were pretreated with ESI-05, an inhibitor of EPAC2 for 1 h, and then incubated with dibutyrylcAMP (db-cAMP) for 48 h. The expression of both a and b subunits of HCG, cholesterol side-chain cleavage enzyme (P450scc), syncytins 1 and 2 was analyzed by real-time RT- PCR. The level of HCG and P4 in the culture media was determined by immunoblotting and ELISA, respectively. Changes in EPAC2-mediated signaling