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Yuta Kasahara Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

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Hiroshi Kishi Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

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Ryo Yokomizo Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

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Aikou Okamoto Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

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aromatization of androgens to estrogens. In a study using luteinized granulosa cells (GCs) collected from IVF-ET (in vitro fertilization - embryo transfer) cases, E 2 secretion was increased, unaffected, or decreased by alcohol intake; in one study, ethanol

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Yan-Guang Wu The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA

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David H Barad The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA
The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA
The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA

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Vitaly A Kushnir The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA
The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA

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Emanuela Lazzaroni The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA

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Qi Wang The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA

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David F Albertini The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA
The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA

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Norbert Gleicher The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA
The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA
The Center for Human Reproduction (CHR), Foundation for Reproductive Medicine, Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Department of Molecular and Integrative Physiology, Stem Cell Biology and Molecular Embryology Laboratory, 21 East 69th Street, New York, New York 10021, USA

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outcomes (5). Specifically, we predicted that changes in immediate ovaria environments of oocytes, represented by granulosa cells (GCs), should be identifiable by comparing cell function at different maternal ages. Rapid declines in IVF pregnancy rates

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Christopher A Price Faculty of Veterinary Medicine, Centre de recherche en reproduction animale, University of Montreal, 3200 rue Sicotte, St‐Hyacinthe, Quebec, Canada J2S 7C6

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proteins called FGF homologous factors) that are grouped into subfamilies based on sequence homology ( Itoh & Ornitz 2004 ). It has been recognized for over 20 years that FGF2 acts on granulosa cells to promote cell proliferation and decrease apoptosis and

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Cecilia Verga Falzacappa Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy
Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Eleonora Timperi Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Barbara Bucci Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Donatella Amendola Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Piero Piergrossi Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Davide D'Amico Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Maria Giulia Santaguida Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Marco Centanni Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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Silvia Misiti Dipartimento di Medicina Sperimentale, Centro Ricerca, Dipartimento di Medicina Molecolare, Dipartimento di Scienze e Biotecnologie Medico Chirurgiche, Cattedra di Endocrinologia, Sapienza Università di Roma, c/o Servizio Speciale Malattie della Tiroide, Viale Regina Elena 324, 00161 Rome, Italy

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-related depletion of ovarian follicles and granulosa cells leading to oligoamenorrhea and subsequent chemotherapy-induced amenorrhea (CIA). This condition can be strongly invalidating when occurring in premenopausal women, being related to a rapid depletion of the

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Lucie Tosca Unité de Physiologie de la Reproduction et des Comportements and
Station de Recherches Avicoles, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
INSERM UMR S671, Centre Biomédical des Cordeliers, Université Pierre et Marie Curie-Paris 6, Paris F-75006, France

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Sabine Crochet Unité de Physiologie de la Reproduction et des Comportements and
Station de Recherches Avicoles, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
INSERM UMR S671, Centre Biomédical des Cordeliers, Université Pierre et Marie Curie-Paris 6, Paris F-75006, France

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Pascal Ferré Unité de Physiologie de la Reproduction et des Comportements and
Station de Recherches Avicoles, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
INSERM UMR S671, Centre Biomédical des Cordeliers, Université Pierre et Marie Curie-Paris 6, Paris F-75006, France

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Fabienne Foufelle Unité de Physiologie de la Reproduction et des Comportements and
Station de Recherches Avicoles, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
INSERM UMR S671, Centre Biomédical des Cordeliers, Université Pierre et Marie Curie-Paris 6, Paris F-75006, France

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Sophie Tesseraud Unité de Physiologie de la Reproduction et des Comportements and
Station de Recherches Avicoles, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
INSERM UMR S671, Centre Biomédical des Cordeliers, Université Pierre et Marie Curie-Paris 6, Paris F-75006, France

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Joëlle Dupont Unité de Physiologie de la Reproduction et des Comportements and
Station de Recherches Avicoles, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
INSERM UMR S671, Centre Biomédical des Cordeliers, Université Pierre et Marie Curie-Paris 6, Paris F-75006, France

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& Hertelendy 1985 ). In the hen layerovary, as in mammals, theca and granulosa cells can be easily isolated from developing follicles. The granulosa cells from the largest follicles produce large amounts of progesterone, but unlike the mammalian granulosa cells

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L J Spicer Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317, USA

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P Y Aad Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317, USA

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D Allen Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317, USA

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S Mazerbourg Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317, USA

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A J Hsueh Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma 74078, USA
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317, USA

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Introduction During ovarian follicular development, granulosa cell proliferation and differentiation are influenced by the gonadotropins and different intraovarian factors secreted by both the oocyte and the surrounding somatic cells

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E C Chin Reproduction and Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK

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T E Harris Reproduction and Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK

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D R E Abayasekara Reproduction and Development Group, Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK

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/PKA system as human granulosa cells undergo luteinization and acquire the capacity to secrete large quantities of progesterone. Materials and Methods Materials Human luteinizing hormone (hLH; NIDDK-hLH-B-SIAFP-2 (6100

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Alice Bongrani UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Namya Mellouk UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Christelle Ramé UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Marion Cornuau Department of Reproductive Medicine and Biology, University Hospital of Tours, Tours, France

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Fabrice Guerif UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France
Department of Reproductive Medicine and Biology, University Hospital of Tours, Tours, France

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Pascal Froment UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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Joëlle Dupont UMR 85 Physiology of Reproduction and Behaviour, National Research Institute for Agriculture, Food and Environment (INRAE) Centre Val de Loire, Nouzilly, France

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selected siRNA #693 for subsequent experiments. Table 4 siRNAs used for cell transfection in in vitro assessment of granulosa cells proliferation, viability and steroidogenesis. siRNA Forward sequence Reverse sequence Provided by

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Michelle Myers
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Sander van den Driesche
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Alan S McNeilly Obstetrics and Gynaecology, MRC Human Reproductive Sciences Unit, Department of Reproductive and Developmental Sciences, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

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W Colin Duncan
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. Luteinisation, the process whereby follicular granulosa cells differentiate into the granulosa-lutein cells of the corpus luteum involves marked and disparate morphological, biochemical and cellular changes. The granulosa cells become terminally differentiated

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Susan M Quirk Department of Animal Science, Cornell University, Ithaca, New York 14850, USA

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Robert G Cowan Department of Animal Science, Cornell University, Ithaca, New York 14850, USA

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Rebecca M Harman Department of Animal Science, Cornell University, Ithaca, New York 14850, USA

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granulosa cells from atretic subordinate follicles are more sensitive to FasL-induced apoptosis than cells from healthy dominant follicles ( Porter et al. 2000 ). Removal of serum from the media of cultured bovine granulosa cells increases expression of

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