title: Effect of antiprogesterone RU486 on VEGF expression and blood vessel remodeling on ovarian follicles before ovulation.
abstract: BACKGROUND
  The success of ovarian follicle growth and ovulation is strictly related to the development of an adequate blood vessel network required to sustain the proliferative and endocrine functions of the follicular cells. Even if the Vascular Endothelial Growth Factor (VEGF) drives angiogenesis before ovulation, the local role exerted by Progesterone (P₄) remains to be clarified, in particular when its concentration rapidly increases before ovulation.
  
  
  OBJECTIVE
  This in vivo study was designed to clarify the effect promoted by a P₄ receptor antagonist, RU486, on VEGF expression and follicular angiogenesis before ovulation, in particular, during the transition from pre to periovulatory follicles induced by human Chorionic Gonadotropins (hCG) administration.
  
  
  METHODS
  Preovulatory follicle growth and ovulation were pharmacologically induced in prepubertal gilts by combining equine Chorionic Gonadotropins (eCG) and hCG used in the presence or absence of RU486. The effects on VEGF expression were analyzed using biochemical and immunohistochemical studies, either on granulosa or on theca layers of follicles isolated few hours before ovulation. This angiogenic factor was also correlated to follicular morphology and to blood vessels architecture.
  
  
  CONCLUSIONS
  VEGF production, blood vessel network and follicle remodeling were impaired by RU486 treatment, even if the cause-effect correlation remains to be clarified. The P₄ antagonist strongly down-regulated theca VEGF expression, thus, preventing most of the angiogenic follicle response induced by hCG. RU486-treated follicles displayed a reduced vascular area, a lower rate of endothelial cell proliferation and a reduced recruitment of perivascular mural cells. These data provide important insights on the biological role of RU486 and, indirectly, on steroid hormones during periovulatory follicular phase. In addition, an in vivo model is proposed to evaluate how periovulatory follicular angiogenesis may affect the functionality of the corpus luteum (CL) and the success of pregnancy.
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Annunziata
authors.initials: A
authors.lastname: Mauro
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Martelli
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Berardinelli
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Russo
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bernabò
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Di Giacinto
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Mattioli
authors.affiliation: Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Barboni
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003338:Corpus Luteum / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology*; D018919:Neovascularization, Physiologic; D009928:Organ Specificity; D006080:Ovarian Follicle / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010060:Ovulation; D011374:Progesterone / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034421:Sus scrofa; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D006727:Hormone Antagonists; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D015735:Mifepristone; D011374:Progesterone
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