title: Nitric oxide induces gelatinase A (matrix metalloproteinase 2) during rat embryo implantation.
abstract: OBJECTIVE
  To evaluate a reciprocal signaling interaction initiated by embryo-derived nitric oxide (NO) to facilitate implantation by increased production of gelatinase A (matrix metalloproteinase 2, MMP2) in uterine stroma.
  
  
  METHODS
  Experimental animal studies.
  
  
  METHODS
  Reproductive-physiology research laboratory.
  
  
  METHODS
  Female syngeneic Wistar rats aged 14 weeks.
  
  
  METHODS
  Vaginal smears to confirm pregnancy. Oviductal ligature to avoid the descent of blastocysts to the uterine lumen. Plasma exudation assays to locate uterine blastocyst implantation sites. Organ cultures treated with NO donors and nitric oxide synthase (NOS) inhibitors.
  
  
  METHODS
  Expression of MMP2 and NO was assessed by Western blot and zymography of tissue extracts and by immunofluorescence of tissue sections.
  
  
  RESULTS
  An increase in MMP2 activity was found in uterine extracts in early pregnant rats and was concentrated at implantation sites. Immunolocalization experiments showed that inducible NOS was expressed on the surface of the implanting blastocyst adjacent to the uterine epithelium at the sites of increased MMP2 expression. In organ culture experiments, NO donors were found to increase, whereas NOS inhibitors were found to decrease MMP2 activity in uterine tissue sections.
  
  
  CONCLUSIONS
  Blastocyst-derived NO contributes to the production of uterine-derived MMP2, an essential component of implantation and initiation of placentation.
authors.affiliation: Centro de Estudios Farmacológicos y Botánicos, Departamento de Fisiología de la Reproducción, Buenos Aires, Argentina. vnovaro@lbl.gov
authors.forename: Virginia
authors.initials: V
authors.lastname: Novaro
authors.forename: Carolina
authors.initials: C
authors.lastname: Pustovrh
authors.forename: Alejandro
authors.initials: A
authors.lastname: Colman-Lerner
authors.forename: Derek
authors.initials: D
authors.lastname: Radisky
authors.forename: Fabiana
authors.initials: F
authors.lastname: Lo Nostro
authors.forename: Dante
authors.initials: D
authors.lastname: Paz
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
authors.forename: Elida
authors.initials: E
authors.lastname: González
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D010064:Embryo Implantation / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000201:enzymology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020030:Nitric Oxide Donors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D020778:Matrix Metalloproteinase 2