title: Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in an ovarian hyperstimulation syndrome (OHSS) animal model: implications for treatment of OHSS with dopamine receptor 2 agonists.
abstract: OBJECTIVE
  To explore whether a dopamine receptor 2 agonist (D2-ag) can prevent ovarian hyperstimulation syndrome (OHSS) in a rat model by decreasing ovarian vascular endothelial growth factor (VEGF) production.
  
  
  METHODS
  Experimental study in an OHSS animal model.
  
  
  METHODS
  University-affiliated infertility center.
  
  
  METHODS
  Immature Wistar rats.
  
  
  METHODS
  Immature rats were stimulated with gonadotropins to mimic OHSS and treated with a D2-ag and/or D2-antagonists (D2-ant). Vascular permeability (VP) was measured at the endpoint, and ovaries were collected to assess the effects of these drugs on VEGF production.
  
  
  METHODS
  VP was estimated by measuring the peritoneal extravasation of a previously injected dye. Ovarian VEGF mRNA expression and VEGF protein levels were assessed by quantitative real-time PCR and Western blots, respectively.
  
  
  RESULTS
  The D2-ag exerted a reduction in VP that was associated with a drastic decrease in VEGF protein production in OHSS rat ovaries. The effects of this D2-ag on VP and VEGF protein levels were partially reversed by concomitant administration of a D2-ant. Ovarian VEGF mRNA expression levels were unaffected by these drugs in OHSS rats.
  
  
  CONCLUSIONS
  D2-ags prevent increased VP in OHSS rats by decreasing ovarian VEGF production, very likely through a D2-mediated post-transcriptional mechanism. Given the dose-dependent inhibitory effect of D2-ags on ovarian VEGF production reported herein, we infer that current OHSS therapies used in humans may be improved by increasing the intraovarian concentration of D2-ags in these patients.
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Ferrero
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: García-Pascual
authors.affiliation: IVI-Madrid, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gaytán
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Cordoba, Cordoba, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Morales
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, University of Cordoba, Cordoba, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gaytán
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pellicer
authors.affiliation: Fundación IVI, Instituto Universitario IVI/INCLIVA, Valencia, Spain. Electronic address: raul.gomez@ivi.es.
authors.forename: Raúl
authors.initials: R
authors.lastname: Gómez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016471:Ovarian Hyperstimulation Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C581293:DRD2 protein, human; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: OHSS; VEGF; animal model; dopamine receptor 2 agonists