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    <journal-meta>
      <journal-id journal-id-type="nlm-ta">J Reprod Infert</journal-id>
      <journal-id journal-id-type="publisher-id">arij001</journal-id>
      <journal-title-group>
        <journal-title>Journal of Reproduction &amp; Infertility</journal-title>
      </journal-title-group>
      <issn pub-type="ppub">2228-5482</issn>
      <issn pub-type="epub">2251-676X</issn>
      <publisher>
        <publisher-name>Avicenna Research Institute</publisher-name>
      </publisher>
    </journal-meta>

    <article-meta>
      <article-id pub-id-type="publisher-id">jri713</article-id>
      <article-id pub-id-type="doi"></article-id>
      <article-id pub-id-type="pmid"></article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
             <subject></subject> 
        </subj-group>
        <subj-group>
            <subject></subject>
        </subj-group> 
      </article-categories>
      <title-group>
        <article-title>Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized Mouse Model</article-title>
      </title-group>
        <contrib-group><contrib contrib-type="author"><name><surname>Tessaro</surname><given-names>Irene</given-names></name></contrib><aff>Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy</aff><aff>Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Ortopedico Galeazzi, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Modina</surname><given-names>Silvia</given-names></name></contrib><aff>Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy</aff><aff>Interdepartmental Centre for the Study of Biological Effects of Nano-Concentrations (CREBION), University of Milan, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Lodde</surname><given-names>Valentina </given-names></name></contrib><aff>Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Sivelli</surname><given-names>Giulia</given-names></name></contrib><aff>Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Franciosi</surname><given-names>Federica</given-names></name></contrib><aff>Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Terzaghi</surname><given-names>Laura</given-names></name></contrib><aff>Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Luchini</surname><given-names>Patrizia</given-names></name></contrib><aff>Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Rumio</surname><given-names>Cristiano</given-names></name></contrib><aff>Interdepartmental Centre for the Study of Biological Effects of Nano-Concentrations (CREBION), University of Milan, Milan, Italy</aff><aff>Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy</aff></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Luciano</surname><given-names>Alberto</given-names></name></contrib><aff>Reproductive and Developmental Biology Laboratory, Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy</aff><aff>Interdepartmental Centre for the Study of Biological Effects of Nano-Concentrations (CREBION), University of Milan, Milan, Italy</aff></contrib-group>
      <pub-date pub-type="ppub">
        <day></day>
        <month></month>
        <year></year>
      </pub-date>
      <pub-date pub-type="epub">
        <day></day>
        <month></month>
        <year></year>
      </pub-date>
      <volume>18</volume>
      <issue>3</issue>
      <fpage>288</fpage>
      <lpage>298</lpage>
      <history>
        <date date-type="received">
          <day>15</day>
          <month>1</month>
          <year>2017</year>
        </date>
        <date date-type="accepted">
          <day>8</day>
          <month>4</month>
          <year>2017</year>
        </date>
      </history>
      <abstract>
      <p>
      &lt;p&gt;Background: Polycystic-ovary syndrome (PCOS) is a reproductive illness characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice, it was demonstrated that the oral administration of incremental dose of follicle stimulating hormone (FSH) attenuated some of PCOS characteristics. This work aimed to study the effect of ultra-low doses of combined FSH and progesterone orally administered on PCOS murine model. Moreover, the effect of sequential kinetic activation of administered hormones was tested.&lt;br /&gt;
Methods: Thirty-two female mice were used as animal model (four groups of eight animals each). Mice were hyperandrogenized by injection of dehyidroepiandro-sterone diluted in sesame oil. Control group received only oil. Simultaneously, each animal daily received per os an activated or a not-activated combination of FSH (0.44 &lt;em&gt;pg&lt;/em&gt;) plus progesterone (0.44 &lt;em&gt;pg&lt;/em&gt;) or saline solution as control. Serum testosterone, estradiol, progesterone and luteinizing hormone were analyzed as endocrine markers and a morphological study of antral follicle was conducted. Data were analyzed by one-way ANOVA, followed by multiple comparison test. The p&amp;lt;0.05 was considered significant.&lt;br /&gt;
Results: Dehyidroepiandrosterone treatment increased both estradiol and progesterone serum levels, besides testosterone, while reduced luteinizing hormone (p&amp;lt;0.05); histological examination revealed an increase of cystic follicles (p&amp;lt;0.05). Irrespective of activation, the combined FSH and progesterone treatments restored estradiol level (p&amp;gt;0.05 &lt;em&gt;vs.&lt;/em&gt; control group) and reduced cystic signs in the follicles (p&amp;lt;0.05 &lt;em&gt;vs&lt;/em&gt;. dehyidroepiandrosterone treatment).&lt;br /&gt;
Conclusion: This study indicate that ultra-low doses of FSH and progesterone orally administrated can reduce the sternness of PCOS in the mouse model and open a route for the study of innovative approaches for PCOS treatment.&lt;/p&gt;

      </p>
      </abstract>
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