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Derek S Boeldt Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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Mary A Grummer Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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Ronald R Magness Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA
Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA
Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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Ian M Bird Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA
Perinatal Research Laboratories, Department of Pediatrics, Department of Animal Sciences, Department of Obstetrics and Gynecology, School Medicine and Public Health, University of Wisconsin–Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA

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. Results from our studies to date have indicated that ATP (working through heptahelical P2Y2 receptors) and vascular endothelial growth factor (VEGF) (working through VEGF receptor 2 (VEGFR2)) in particular both stimulate comparatively low NO production in

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Rosa Chung
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Bruce K Foster School of Pharmacy and Medical Sciences, Department of Orthopaedic Surgery, Sansom Institute for Health Research, University of South Australia, City East Campus, GPO Box 2471, Adelaide, South Australia 5001, Australia

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Cory J Xian
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fracture repair ( Carano & Filvaroff 2003 , Keramaris et al . 2008 , Tang et al . 2012 ). Although fibroblast growth factor 2, platelet-derived growth factor (PDGFBB) and vascular endothelial growth factor (VEGF) have all been associated as angiogenic

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Siobhan M Donnelly
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Bao Tran Nguyen
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Scott Rhyne
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Jordan Estes
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Subrina Jesmin Department of Biology, Appalachian State University, Department of Internal Medicine, Tsukuba University, Rankin Science North Building N219, 572 River Street, Boone, North Carolina 28608, USA

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Chishimba Nathan Mowa
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likely to be regulated by multiple factors, either in a synergistic or complementary manner. It is interesting to note that, like relaxin, vascular endothelial growth factor ( Vegf ) expression is, in part, induced by estrogen both in the uterus and in

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M A J Hervé INSERM U553, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
INSERM U716, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
Unité INSERM 540, Montpellier, France

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G Meduri INSERM U553, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
INSERM U716, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
Unité INSERM 540, Montpellier, France

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F G Petit INSERM U553, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
INSERM U716, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
Unité INSERM 540, Montpellier, France

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T S Domet INSERM U553, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
INSERM U716, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
Unité INSERM 540, Montpellier, France

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G Lazennec INSERM U553, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
INSERM U716, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
Unité INSERM 540, Montpellier, France

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S Mourah INSERM U553, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
INSERM U716, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
Unité INSERM 540, Montpellier, France

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M Perrot-Applanat INSERM U553, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
INSERM U716, Institut Universitaire d’Hématologie, Hôpital Saint-Louis/Bâtiment INSERM, 1 avenue Claude Vellefaux, 75010 Paris, France
Unité INSERM 540, Montpellier, France

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progesterone. Previous studies have demonstrated that E 2 increases the secretion of vascular endothelial growth factor (VEGF) in uterine cells ( Cullivan-Bove & Koos 1993 , Shifren et al. 1996 , Bausero et al. 1998 ); this factor has emerged as one of

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Michal Silber Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Department of OB/GYN, Meir Medical Center, Kfar Saba, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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Irit Miller Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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Hadas Bar-Joseph Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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Ido Ben-Ami IVF and Fertility Unit, Department of OB/GYN, Shaare Zedek Medical Center, Jerusalem, Israel
The Hebrew University Medical School of Jerusalem, Jerusalem, Israel

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Ruth Shalgi Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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and GCs, PCOS is considered a chronic low-grade inflammatory disorder, associated with obesity, IR, and hyperandrogenism ( Schmidt et al. 2014 , Shorakae et al. 2015 , Peng et al. 2016 ). Vascular endothelial growth factor (VEGF) is an

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Chiara Onofri Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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Marily Theodoropoulou Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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Marco Losa Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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Eberhard Uhl Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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Manfred Lange Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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Eduardo Arzt Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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Günter K Stalla Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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Ulrich Renner Max-Planck-Institute of Psychiatry, Neuroendocrinology Group, Kraepelinstr. 10, D-80804 Munich, Germany
Istituto San Raffaele, Neurosurgical Department, Milano, Italy
Ludwig-Maximilians University, Neurosurgical Department, Munich, Germany
Klinikum Villingen-Schwenningen, Neurosurgical Department, Villingen-Schwenningen, Germany
Laboratorio de Fisiología y Biología Molecular, Departamento Ciencias Biológicas, FCEN-Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina

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involved in neovascularization, such as fibroblast growth factor-2, platelet-derived growth factors, transforming growth factor-β and members of the vascular endothelial growth factor (VEGF) family ( Carmeliet 2003 , Ferrara 2004 ). VEGF-A is one

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Achim Lother Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Lisa Deng Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Michael Huck Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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David Fürst Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Jessica Kowalski Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Jennifer S Esser Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Martin Moser Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Christoph Bode Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Lutz Hein Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany

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endothelial growth factor (VEGF) ( Carmeliet & Jain 2011 ). In the heart, VEGF is produced by cardiac myocytes in response to hypoxia-induced factor 1α signaling ( Oka et al. 2014 ). VEGF stimulates angiogenesis by acting on the VEGF receptor 2 (VEGFR2) on

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Eriko Furube Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

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Tetsuya Mannari Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

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Shoko Morita Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

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Kazunori Nishikawa Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

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Ayaka Yoshida Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

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Masanobu Itoh Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

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Seiji Miyata Department of Applied Biology, Department of Anatomy and Neuroscience, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan

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fenestrated feature ( Norsted et al . 2008 , Mullier et al . 2010 , Ciofi et al . 2009 , 2011 , Morita & Miyata 2012 ). However, we have recently shown the occurrence of vascular endothelial growth factor (VEGF)-dependent continuous angiogenesis and the

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DE Clark
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SK Smith
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D Licence
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AL Evans
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DS Charnock-Jones
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Angiogenesis and vascular transformation are important processes in the normal development of the placenta. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor and is thought to be important for placental development. Recently several new members of this family have been described. In this study we used in situ hybridisation to localise which cells in the placenta expressed mRNA for VEGF, placenta growth factor (PlGF), VEGF-B and VEGF-C. We were unable to find any message for either VEGF-B or VEGF-C in the placenta, suggesting that only low levels are produced which this method was unable to detect. The mRNA encoding VEGF was found to be produced by cells within the villous mesenchyme, decidual macrophages and decidual glands but, in contrast to our previous findings, not by trophoblast. The mRNA encoding PlGF was produced in large amounts by villous cytotrophoblast, syncytiotrophoblast and extravillous trophoblast. The mRNAs encoding VEGF and PlGF were thus not co-localised and it appears that there is unlikely to be any significant production of VEGF/PlGF heterodimer in the placenta.

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Ebrahim Asadi Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, Iran

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Atefeh Najafi Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, Iran

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Ashraf Moeini Department of Gynecology and Obstetrics, Arash Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Reihaneh Pirjani Department of Gynecology and Obstetrics, Arash Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Gholamreza Hassanzadeh Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, Iran

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Saideh Mikaeili Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, Iran

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Ensieh Salehi Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, Iran

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Emmanuel Adutwum School of Medicine, Tehran University of Medical Science, Tehran, Iran

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Mansoureh Soleimani Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
Department of Anatomical Sciences, School of Medicine, Iran University of Medical Science, Tehran, Iran

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Fariba Khosravi One Fertility, Kitchener, Ontario, Canada

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Mahmood Barati Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Farid Abolhassani Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, Iran

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.14 0.45 ± 0.16 2 95.71 ± 29.11 0.40 ± 0.18 VEGF 4 114.71 ± 29.67 0.48 ± 0.20* 6 143.14 ± 48.80* 0.63 ± 0.20** 2 110.14 ± 30.42 0.39 ± 0.14 VEGF + fetuin 4 132.00 ± 43.00* 0.47 ± 0.14 6

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