Expression and function of placental uric acid transporter GLUT9

s / Placenta 36 (2015) A1eA60 A55 underperfusion were dominant in patients with PE regardless of FGR compared to patients with sole FGR (52.8% vs 18.8%, p1⁄4 0.033). In addition, maternal demographic characteristics analysis show statistically significant association between high BMI and PE, regardless of FGR (p 1⁄4 0.01). Conclusion: Dominant placental findings of FGR and PE in preterm were villous of fetal vascular thrombo-occlusive disease and vascular lesions consistent with maternal underperfusion, respectively. In addition, considering statistically significance, BMI is likely to be a risk factor of PE. P2.56. EXPRESSION AND FUNCTION OF PLACENTAL URIC ACID TRANSPORTER GLUT9 Benjamin P. Luscher , Marc U. Baumann , Camilla Marini , Matthias A. Hediger , Christiane Albrecht , Bruno Stieger , Daniel V. Surbek . Department of Obstetrics and Gynecology, University Hospital of Bern, Bern, Switzerland; Department of Clinical Research, University of Bern, Bern, Switzerland; 3 Institute for Biochemistry and Molecular Medicine, Bern, Switzerland; Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland Objectives: Uric acid is increased in women with pre-eclampsia and is believed to play a significant role in its pathogenesis. Hyperuricemia originates from renal and placental dysregulation and may lead to long-term maternal cardiovascular risk and to fetal programming. In the placenta, the regulation of uric acid transport is not yet understood, but is likely to be predominantly regulated by glucose transporter-9 (GLUT9). The aim of this study was to characterize placental GLUT9 expression and regulation. Methods: Humanplacental GLUT9 expressionwas determined using novel self-raised antibodies against human isoforms GLUT9a and -b. Uric acid transport activity of both GLUT9 isoforms using electrophysiological techniques was assessed in the Xenopus GLUT9 over-expression system. Results: Both GLUT9 isoforms are present in the microvillus membrane (MVM) of the syncytiotrophoblast cells, but not in the basal membrane (BM). In the Xenopus oocytes GLUT9 overexpression system replacing chloride with iodine resulted in a complete loss of uric acid transport for GLUT9a. Conclusions: Our results show that GLUT9 isoforms are expressed exclusively in the microvillus (apical) membrane of the syncytiotrophoblast, suggesting that GLUT9 is responsible for uric acid transport in the placenta. Furthermore, GLUT9 uric acid transport activity is iodine-regulated. Since placental tissue iodine levels are decreased in pre-eclampsia1, placental iodine-mediated Glut9 dysregulation might contribute to hyperuricemia in pre-eclampsia. P2.57. WNT5A CAN BE INVOLVED IN THE PATHOGENESIS OF PREECLAMPSIA THROUGH MODULATION OF SPIRAL ARTERY REMODELLING AND PRO-AND ANTI-ANGIOGENIC FACTORS Mari Ujita, Eiji Kondoh, Kaoru Kawasaki, Yoshitsugu Chigusa, Mai Sato, Hiroshi Takai, Hikaru Kiyokawa, Haruta Mogami, Ikuo Konishi. Kyoto University, Kyoto, Japan Objectives: Wnt signaling plays an important role in murine placental development. However, the role of Wnt signaling in preeclamptic placenta has not been clarified yet. This study aims to investigate the influence of Wnt signaling on the pathogenesis of preeclampsia(PE), particularly on uterine artery remodeling and angiogenesis-related gene expressions. Methods: Human placentas were obtained from preeclamptic and healthy women who underwent cesarean section. The activity of Wnt signaling was analysed by quantitative(q)RT-PCR, Western blotting and immunohistochemistry. Expressions of angiogenesis-related genes were also examined in PE and healthy placentas. HTR8/SVneo trophoblast cells(HTR cells) were cultured on Matrigel, and the effect of Wnt5a was evaluated. HTR cells were cultured with recombinant(r)Wnt5a and the changes of sFlt1, PlGF and TGFb expressions were evaluated by qRT-PCR. HTR cells were also culturedwith thrombin (10U/ml) with or without 24H treatment of rWnt5a, and sFlt1 and PlGF expressions were investigated. Results: The expression of Wnt5a as well as TGFb3 and PlGF were significantly suppressed in the PEplacentas.Wnt5aupregulated TGFb1, TGFb3, and PlGF mRNA expressions of HTR cells but didn’t decrease sFlt1 expression. Thrombin increased sFlt1 expression and decreased PlGF expression in HTR cell, while rWnt5a counteracted the impact of thrombin. Tube formation of HTR cells was enhanced by rWnt5a and was suppressed by Wnt5a-siRNA. Conclusion: Wnt5a may contribute to the pathogenesis of PE by controlling the uterine artery remodelling and the releasing of angiogenesisrelated factors. P2.58. FIRST TRIMESTER DECIDUAL STROMAL CELL REGULATION OF TROPHOBLAST CELLS AND THE EFFECT OF TGFb1 Laura James-Allan, Alison Wallace, Guy Whitley, Judith Cartwright. St George's University of London, London, UK Objectives: Decidualisation is the differentiation of endometrial stromal cells into specialised secretory decidual stromal cells (DSC). In pregnancy, DSC control and regulate fetal trophoblast invasion. Pre-eclampsia (PE) is associated with inadequate trophoblast invasion and spiral artery (SA) remodelling. Uterine artery Doppler resistance index (RI) is used as a proxy measure to identify pregnancies with normal (normal RI) or impaired (high RI) SA remodelling. The phenotype of DSC with a high or normal RI and their effect on trophoblast functions was investigated. TGFb1 secretion from high vs normal RI DSC was measured and the effect of TGFb1 on trophoblast was determined. Methods: DSC were isolated from tissue obtained from first trimester terminations of pregnancy screened by uterine artery Doppler ultrasound. DSC were decidualised in vitro using cAMP and medroxyprogesterone 17acetate (MPA); decidualisation was measured by secretion of IGFBP1, PRL and expression of FOXO1. The trophoblast cell line SGHPL-4 was incubated with DSC conditionedmedia (CM) and chemotaxis, apoptosis, proliferation and motility measured. TGFb secretion by DSC was measured by ELISA. Results: Decidualisation of DSC increased secretion of IGFBP1, PRL and FOXO1 (p 10 weeks gestation. DSC CM from pregnancies with high RI had no effect on trophoblast chemotaxis. DSC CM had no effect on trophoblast apoptosis, proliferation or motility. High RI DSC CM had significantly higher levels of TGFb compared to normal RI CM (p < 0.05). Normal RI DSC CM with added recombinant TGFb inhibited trophoblast chemotaxis (p<0.05). Conclusion: The results indicate that DSC from high RI pregnancies secrete higher levels of TGFb, contributing to inhibition of trophoblast chemotaxis. These findings may be important in understanding aberrant trophoblast invasion in pregnancies where SA remodelling is impaired. P2.59. IMMUNOHISTOCHEMICAL EXPRESSION OF ANGIOGENIC AND IMMUNOLOGICAL FACTORS IN PLACENTA WITH PREECLAMPSIA AND/ OR FETAL GROWTH RESTRICTION Naoyuki Iwahashi, Tamaki Yahata, Mika Mizoguchi, Sakiko Nanjyo, Madoka Yamamoto, Yuko Tanizaki, Aya Kobayashi, Michihisa Shiro, Nami Ota, Yasushi Mabuchi, Shigetaka yagi, Sawako Minami, Kazuhiko Ino. Wakayama Medical University, Wakayama, Japan Objectives: Impaired placental angiogenesis is associated with preeclampsia (PE) and fetal growth restriction (FGR). Immunosuppressive factors such as indoleamine 2, 3-dioxygenase (IDO) or TGF-bmay also play a role in placental development. Our objective was to determine the differences in fms-like tyrosine kinase receptor-1 (Flt-1), vascular endothelial growth factor (VEGF), IDO, and TGF-b expressions among normal, preeclampsia (PE), and fetal growth restriction (FGR) placentas. Methods: Immunohistochemical studies were performed in human placenta from the 3rd trimester of pregnancies complicated with either PE