title: Peritoneal fluid reduces angiogenesis-related microRNA expression in cell cultures of endometrial and endometriotic tissues from women with endometriosis.
abstract: Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent gynecological diseases. It has been suggested that modifications of both endometrial and peritoneal factors could be implicated in this disease. Endometriosis is a multifactorial disease in which angiogenesis and proteolysis are dysregulated. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the protein expression and may be the main regulators of angiogenesis. Our hypothesis is that peritoneal fluid from women with endometriosis could modify the expression of several miRNAs that regulate angiogenesis and proteolysis in the endometriosis development. The objective of this study has been to evaluate the influence of endometriotic peritoneal fluid on the expression of six miRNAs related to angiogenesis, as well as several angiogenic and proteolytic factors in endometrial and endometriotic cell cultures from women with endometriosis compared with women without endometriosis.
  
  
  METHODS
  Endometrial and endometriotic cells were cultured and treated with endometriotic and control peritoneal fluid pools. We have studied the expression of six miRNAs (miR-16, -17-5p, -20a, -125a, -221, and -222) by RT-PCR and protein and mRNA levels of vascular endothelial growth factor-A, thrombospondin-1, urokinase plasminogen activator and plasminogen activator inhibitor-1 by ELISA and qRT-PCR respectively.
  
  
  RESULTS
  Control and endometriotic peritoneal fluid pools induced a significant reduction of all miRNAs levels in endometrial and endometriotic cell cultures. Moreover, both peritoneal fluids induced a significant increase in VEGF-A, uPA and PAI-1 protein levels in all cell cultures without significant increase in mRNA levels. Endometrial cell cultures from patients treated with endometriotic peritoneal fluid showed lower expression of miRNAs and higher expression of VEGF-A protein levels than cultures from controls. In conclusion , this "in vitro" study indicates that peritoneal fluid from women with endometriosis modulates the expression of miRNAs that could contribute to the angiogenic and proteolytic disequilibrium observed in this disease.
authors.affiliation: Grupo de Hemostasia, Trombosis, Arteriosclerosis y Biología Vascular, Instituto Investigación Sanitaria Hospital La Fe, Valencia, Spain.
authors.forename: Aitana
authors.initials: A
authors.lastname: Braza-Boïls
authors.forename: Juan
authors.initials: J
authors.lastname: Gilabert-Estellés
authors.forename: Luis A
authors.initials: LA
authors.lastname: Ramón
authors.forename: Juan
authors.initials: J
authors.lastname: Gilabert
authors.forename: Josep
authors.initials: J
authors.lastname: Marí-Alexandre
authors.forename: Melitina
authors.initials: M
authors.lastname: Chirivella
authors.forename: Francisco
authors.initials: F
authors.lastname: España
authors.forename: Amparo
authors.initials: A
authors.lastname: Estellés
mesh_terms: D000328:Adult; D001202:Ascitic Fluid / Q000378:metabolism*; D018929:Cell Culture Techniques; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005342:Fibrinolysis / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D014568:Urokinase-Type Plasminogen Activator