title: Evaluation of the potential therapeutic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of endometriosis.
abstract: OBJECTIVE
  To assess the therapeutic potential of polyinosine-polycytidylic acid, a double-stranded RNA molecule with selective proapoptotic and antiangiogenic activity, complexed with polyethyleneimine (pIC(PEI)) in treating endometriosis.
  
  
  METHODS
  A heterologous mouse model of endometriosis was created by injecting human endometrial fragments into the peritoneum. Endometrial fragments were engineered to express the fluorescent protein mCherry as a reporter to monitor status over the course of the 4-week study.
  
  
  METHODS
  University-affiliated infertility center.
  
  
  METHODS
  Ovariectomized and hormone-replaced nude mice (n = 30) injected with fluorescent-labeled human endometrial fragments at 4-6 weeks of age.
  
  
  METHODS
  Animals (n = 10 per group) were injected with vehicle (control), the anti-VEGF compound CBO-P11 (0.6 mg/kg), or pIC(PEI) (0.6 mg/kg) twice weekly over the course of 4 weeks.
  
  
  METHODS
  Variations in the size of endometriotic implants were estimated by quantifying the expression of mCherry throughout the course of the experiment. Neovascularization, cellular proliferation, and apoptosis were estimated by quantitative immunofluorescence detection of PECAM, α-SMA, Ki67, and TUNEL.
  
  
  RESULTS
  pIC(PEI) promoted a significant increase in apoptosis and a decrease in neovascularization in human fragments, but did not reduce the size of endometriotic implants.
  
  
  CONCLUSIONS
  While pIC(PEI) treatment had significant antiangiogenic and pro-apoptotic effects in this setting, longer periods of exposure than the ones supported by our heterologous model and/or assays in homologous mouse models of endometriosis may be necessary to detect an effect of this compound on lesion size.
authors: Instituto Universitario IVI/INCLIVA, Valencia, Spain; Fundación IVI, Parque Científico Universidad de Valencia, Paterna, Spain.
authors: Carmen Maria
authors: CM
authors: García-Pascual
authors: Instituto Universitario IVI/INCLIVA, Valencia, Spain.
authors: Jessica
authors: J
authors: Martínez
authors: Departamento de Ginecología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Paula
authors: P
authors: Calvo
authors: Instituto Universitario IVI/INCLIVA, Valencia, Spain; Fundación IVI, Parque Científico Universidad de Valencia, Paterna, Spain.
authors: Hortensia
authors: H
authors: Ferrero
authors: Bioncotech Therapeutics, Paterna, Spain.
authors: Ana
authors: A
authors: Villanueva
authors: Bioncotech Therapeutics, Paterna, Spain.
authors: Mercedes
authors: M
authors: Pozuelo-Rubio
authors: Melanoma Laboratory, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre), Madrid, Spain.
authors: Marisol
authors: M
authors: Soengas
authors: Bioncotech Therapeutics, Paterna, Spain.
authors: Damiá
authors: D
authors: Tormo
authors: Instituto Universitario IVI/INCLIVA, Valencia, Spain; Fundación IVI, Parque Científico Universidad de Valencia, Paterna, Spain.
authors: Carlos
authors: C
authors: Simón
authors: Fundación IVI, Parque Científico Universidad de Valencia, Paterna, Spain; Departamento de Ginecología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors: Antonio
authors: A
authors: Pellicer
authors: Instituto Universitario IVI/INCLIVA, Valencia, Spain. Electronic address: raulgomgal@gmail.com.
authors: Raúl
authors: R
authors: Gómez
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D016228:Endothelial Growth Factors / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D017930:Genes, Reporter; D064593:Heterografts; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D010052:Ovariectomy; D010456:Peptides, Cyclic / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors; D000097573:Red Fluorescent Protein
chemical_list: D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D008164:Luminescent Proteins; D010456:Peptides, Cyclic; D011070:Poly I-C; D011094:Polyethyleneimine; D000097573:Red Fluorescent Protein; C478485:cyclo-VEGI
keywords: Endometriosis; angiogenesis; apoptosis; mouse model; pIC(PEI)