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The effects of vascular endothelial cells on migration of trophoblast cells
Abstracts / Placenta 34 (2013) A1–A17
No.34 STATIN ACTIVATES NRF2 AND INCREASES EXPRESSION IN TROPHOBLAST CELLS
ANTIOXIDANT
GENE
Yoshitsugu Chigusa, Eiji Kondoh, Haruta Mogami, Kaoru Kawasaki, Hikaru Kiyokawa, Mari Ujita, Fumitomo Nishimura, Kohei Fujita, Ikuo Konishi Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Abstract Objective: The placenta has own defensive mechanism against oxidative stress, in which transcription factor Nrf2 plays a central role by regulating antioxidant and cytoprotective genes, such as HO-1, GCLC, and GCLM. Although we previously reported low Nrf2 activation in preeclamptic (PE) placenta despite increasing oxidative stress, its mechanism remains unclear. On the other hand, accumulating evidence indicates statin may be beneficial to PE. However it is presently unknown whether statin is involved in Nrf2 activation in trophoblast cells. The objectives of this study are to clarify the mechanism by which Nrf2 activation is decreased in PE placenta, and to reveal that statin affects Nrf2 activation in vitro. Methods: JAR cells were cultured under 20% or 1% O2 with Nrf2 activator, and Nrf2 activation was examined by Western blotting. JAR cells were treated with simvastatin, and Nrf2 activation and its target genes expression, including HO-1, GCLC, GCLM, were analyzed by Western blotting or RT-PCR. Results: Under hypoxic condition, Nrf2 activation was significantly restrained in JAR cells. Statin treatment demonstrated significant Nrf2 activation, and increased the expression of HO-1, GCLC, and GCLM in JAR cells. Conclusion: Hypoxia is considered one of the causes of low Nrf2 activation in PE placenta. Meanwhile, simvastatin has the effect on Nrf2 activation in JAR cells. The Nrf2 activation by statin may be a novel therapeutic approach for PE. http://dx.doi.org/10.1016/j.placenta.2013.07.047
No.35 A CASE OF VANISHING PARTIAL HYDATIDIFORM MOLE COEXISTENT WITH A LIVE FETUS (HMCF). Nobuhiko Hayashi 1, 2, Qu jia 2, Hirokazu Usui 1, 2, Makio Shozu 1,2
A13
revealed only necrotic tissue in the cyctic region, DNA polymorphism analysis suggested a “Diandric Monogynic”partial mole.Although only a few cases of partial mole with term delivery have been reported, more cases might be misdiagnosed as a spontaneous abortion, probably due to heart beat at early stage in pregnancy. We must think of HMCF when we saw vanishing twin, and patients with HMCF must be monitored to assess for persistent diseases which may occur after a delivery. Genetic analysis is useful to settle the diagnosis of molar pregnancy. http://dx.doi.org/10.1016/j.placenta.2013.07.048
No.36 THE EFFECTS OF VASCULAR ENDOTHELIAL CELLS ON MIGRATION OF TROPHOBLAST CELLS Tomoko Izawa, Keiji Sakai, Mitutoshi Iwashita Kyorin University, Tokyo, Japan
Abstract Background: Trophoblasts migrate and invade into uterine decidua and replace vascular endothelial cells of spiral artery. This replacement reduces a tension of spiral artery and results in increased blood flow to placenta. However, the mechanism of trophoblast migration towards spiral artery has not been elucidated. To test the possibility that vascular endothelial cells produce substances that regulate trophoblast migration, we analyzed effects of endothelial cells on trophoblast migration.Moreover, the effects of progesterone and estrogen on trophoblast migration induced by endothelial cells were analyzed. Methods: Trophoblasts were isolated and cultured from villous tissue which was obtained from elective termination at first trimester with informed consent. Human umbilical vein endothelial cells (HUVECs) were used as endothelial cells. Migration assay was carried out using Boyden-chamber. HUVECs were seeded in the lower chamber and trophoblasts were seeded in the upper chamber. After 48-hour co-culture, migrated trophoblasts were stained and counted. HUVECs were also incubated with medroxyprogesterone acetate (MPA) or estradiol (E2) for 48 hours and then migration assay was performed as the same method. Results: Migrated trophoblasts were increased in proportion to the numbers of HUVECs. MPA (1 x 10-7M) and E2 (1 x 10-9M) stimulated trophoblast migration by 2.4 or 1.6 folds of the control, respectively. Conclusions: These results indicate that HUVECs produce substances that are regulated by placental steroid hormones. These substances might stimulate trophoblast migration and promote remodeling of spiral artery.
1
Department of Obstetrics and Gynecology, Chiba University Hospital, Chiba, Japan; 2 Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
http://dx.doi.org/10.1016/j.placenta.2013.07.049
No.37
Abstract Vanishin twin is not a rare condition in twin pregnancies. Prognosis of live fetuses will be good, if it were term deliveries. The vanishng fetus are usually disappeared, and we do not find those tissues after deliveries. Here, we report a case of “partial” HMCF, which was confirmed by short tandem repeat polymorphism analysis after a full term delivery. We diagnosed dichorionic diamniotic twin at 8 weeks of gestation, one was CRL 16mm, FHB>100bpm, the other was CRL 6mm, FHB<100bpm. At 10 weeks of gestation, the smaller fetus had disappeared and was replaced by a small multi cystic appearance on ultrasound. We suspected a partial hydatidiform mole coexisting with another normal fetus. A live baby girl weighing 3,430g was delivered at 40 weeks of gestation, with Apgar scores of 9 at 1min and 5min, without complications during pregnancy. The delivered placenta appeared normal, but small lesion of multiple vesicles were visible on the membrane. Although histopathological examination
THE ANTI-INFLAMMATORY ROLE OF HOFBAUER CELLS IN THE LESION OF VUE Kentaro Matsuoka 1, Yuki Ito 2, Hideto Iwafuchi 1, Atsuoko Nakazawa 1, Kenichiro Hata 2 1 Department of Pathology National Medical Center for Children and Mothers, Tokyo, Japan; 2 Department of Maternal-Fetal Biology National Research Institute for Child Health and Development, Tokyo, Japan
Abstract Chronic villitis is defined as a chronic inflammatory infiltrate in the chorionic villi. These are divided into two groups, one is an infectious villitis and the other is a so-called villitis of unknown etiology (VUE). In this study,
No.34 STATIN ACTIVATES NRF2 AND INCREASES EXPRESSION IN TROPHOBLAST CELLS
ANTIOXIDANT
GENE
Yoshitsugu Chigusa, Eiji Kondoh, Haruta Mogami, Kaoru Kawasaki, Hikaru Kiyokawa, Mari Ujita, Fumitomo Nishimura, Kohei Fujita, Ikuo Konishi Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Abstract Objective: The placenta has own defensive mechanism against oxidative stress, in which transcription factor Nrf2 plays a central role by regulating antioxidant and cytoprotective genes, such as HO-1, GCLC, and GCLM. Although we previously reported low Nrf2 activation in preeclamptic (PE) placenta despite increasing oxidative stress, its mechanism remains unclear. On the other hand, accumulating evidence indicates statin may be beneficial to PE. However it is presently unknown whether statin is involved in Nrf2 activation in trophoblast cells. The objectives of this study are to clarify the mechanism by which Nrf2 activation is decreased in PE placenta, and to reveal that statin affects Nrf2 activation in vitro. Methods: JAR cells were cultured under 20% or 1% O2 with Nrf2 activator, and Nrf2 activation was examined by Western blotting. JAR cells were treated with simvastatin, and Nrf2 activation and its target genes expression, including HO-1, GCLC, GCLM, were analyzed by Western blotting or RT-PCR. Results: Under hypoxic condition, Nrf2 activation was significantly restrained in JAR cells. Statin treatment demonstrated significant Nrf2 activation, and increased the expression of HO-1, GCLC, and GCLM in JAR cells. Conclusion: Hypoxia is considered one of the causes of low Nrf2 activation in PE placenta. Meanwhile, simvastatin has the effect on Nrf2 activation in JAR cells. The Nrf2 activation by statin may be a novel therapeutic approach for PE. http://dx.doi.org/10.1016/j.placenta.2013.07.047
No.35 A CASE OF VANISHING PARTIAL HYDATIDIFORM MOLE COEXISTENT WITH A LIVE FETUS (HMCF). Nobuhiko Hayashi 1, 2, Qu jia 2, Hirokazu Usui 1, 2, Makio Shozu 1,2
A13
revealed only necrotic tissue in the cyctic region, DNA polymorphism analysis suggested a “Diandric Monogynic”partial mole.Although only a few cases of partial mole with term delivery have been reported, more cases might be misdiagnosed as a spontaneous abortion, probably due to heart beat at early stage in pregnancy. We must think of HMCF when we saw vanishing twin, and patients with HMCF must be monitored to assess for persistent diseases which may occur after a delivery. Genetic analysis is useful to settle the diagnosis of molar pregnancy. http://dx.doi.org/10.1016/j.placenta.2013.07.048
No.36 THE EFFECTS OF VASCULAR ENDOTHELIAL CELLS ON MIGRATION OF TROPHOBLAST CELLS Tomoko Izawa, Keiji Sakai, Mitutoshi Iwashita Kyorin University, Tokyo, Japan
Abstract Background: Trophoblasts migrate and invade into uterine decidua and replace vascular endothelial cells of spiral artery. This replacement reduces a tension of spiral artery and results in increased blood flow to placenta. However, the mechanism of trophoblast migration towards spiral artery has not been elucidated. To test the possibility that vascular endothelial cells produce substances that regulate trophoblast migration, we analyzed effects of endothelial cells on trophoblast migration.Moreover, the effects of progesterone and estrogen on trophoblast migration induced by endothelial cells were analyzed. Methods: Trophoblasts were isolated and cultured from villous tissue which was obtained from elective termination at first trimester with informed consent. Human umbilical vein endothelial cells (HUVECs) were used as endothelial cells. Migration assay was carried out using Boyden-chamber. HUVECs were seeded in the lower chamber and trophoblasts were seeded in the upper chamber. After 48-hour co-culture, migrated trophoblasts were stained and counted. HUVECs were also incubated with medroxyprogesterone acetate (MPA) or estradiol (E2) for 48 hours and then migration assay was performed as the same method. Results: Migrated trophoblasts were increased in proportion to the numbers of HUVECs. MPA (1 x 10-7M) and E2 (1 x 10-9M) stimulated trophoblast migration by 2.4 or 1.6 folds of the control, respectively. Conclusions: These results indicate that HUVECs produce substances that are regulated by placental steroid hormones. These substances might stimulate trophoblast migration and promote remodeling of spiral artery.
1
Department of Obstetrics and Gynecology, Chiba University Hospital, Chiba, Japan; 2 Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan
http://dx.doi.org/10.1016/j.placenta.2013.07.049
No.37
Abstract Vanishin twin is not a rare condition in twin pregnancies. Prognosis of live fetuses will be good, if it were term deliveries. The vanishng fetus are usually disappeared, and we do not find those tissues after deliveries. Here, we report a case of “partial” HMCF, which was confirmed by short tandem repeat polymorphism analysis after a full term delivery. We diagnosed dichorionic diamniotic twin at 8 weeks of gestation, one was CRL 16mm, FHB>100bpm, the other was CRL 6mm, FHB<100bpm. At 10 weeks of gestation, the smaller fetus had disappeared and was replaced by a small multi cystic appearance on ultrasound. We suspected a partial hydatidiform mole coexisting with another normal fetus. A live baby girl weighing 3,430g was delivered at 40 weeks of gestation, with Apgar scores of 9 at 1min and 5min, without complications during pregnancy. The delivered placenta appeared normal, but small lesion of multiple vesicles were visible on the membrane. Although histopathological examination
THE ANTI-INFLAMMATORY ROLE OF HOFBAUER CELLS IN THE LESION OF VUE Kentaro Matsuoka 1, Yuki Ito 2, Hideto Iwafuchi 1, Atsuoko Nakazawa 1, Kenichiro Hata 2 1 Department of Pathology National Medical Center for Children and Mothers, Tokyo, Japan; 2 Department of Maternal-Fetal Biology National Research Institute for Child Health and Development, Tokyo, Japan
Abstract Chronic villitis is defined as a chronic inflammatory infiltrate in the chorionic villi. These are divided into two groups, one is an infectious villitis and the other is a so-called villitis of unknown etiology (VUE). In this study,