title: Augmented Angiogenic Factors Expression via FP Signaling Pathways in Peritoneal Endometriosis.
abstract: Angiogenesis is required for ectopic endometrial tissue growth. Our previous studies showed that prostaglandin F2α(PGF2α) biosynthetic enzymes and receptor were markedly elevated in endometriotic lesions and that PGF2αis a potent angiogenic factor in endothelial cells.
  
  
  
  We sought to determine whether or not the F-prostanoid receptor modulates angiogenesis in ectopic stromal cells.
  
  
  
  Release of angiogenic factors by ectopic endometrial stromal cell primary cultures stimulated with PGF2αand exposed to agents that target PGF2αsignaling was assessed.
  
  
  
  The study was conducted in an immunology laboratory at the Centre Hospitalier Universitaire (Québec City) medical research center.
  
  
  
  Women found to have peritoneal endometriosis during laparoscopy were included in this study.
  
  
  
  Prostaglandin E2, PGF2α, vascular endothelial cell growth factor, and CXC chemokine ligand 8 mRNA and protein; FP prostanoid receptor expression.
  
  
  
  PGF2αmarkedly up-regulated prostaglandin E2, CXC chemokine ligand 8 and vascular endothelial cell growth factor secretion in endometriotic cells. This effect was suppressed in the presence of a specific F-prostanoid antagonist (AL8810) and its signaling pathway was dependent on F-prostanoid receptor variant. PGF2αcan exert its proliferative and angiogenic activities either directly by stimulating endothelial cell proliferation, migration and angiogenesis through F-prostanoid receptor, or indirectly, by stimulating endometriotic stromal cells to produce potent angiogenic factors through either receptor variant.
  
  
  
  These results show for the first time that PGF2αexerts an angiogenic effect on ectopic stromal cells, inducing the secretion of major angiogenic factors via different F-prostanoid signaling pathways. This study suggests a new interpretation of the mechanism underlying endometriosis development involving PGF2αin endometriosis-associated angio-inflammatory changes.
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Halima
authors.initials: H
authors.lastname: Rakhila
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Mahera
authors.initials: M
authors.lastname: Al-Akoum
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Doillon
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lacroix-Pépin
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Leboeuf
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Lemyre
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Akoum
authors.affiliation: Laboratory of Immunology (H.R., M.A.-A., C.D., M.P.), Research Center, Centre Hospitalier Universitaire de Québec, Faculty of Medicine, Laval University, Québec City, Canada; Laboratory of Reproduction (N.L.-P.), Faculty of Medicine, Laval University, Québec City, Canada; Department of Obstetrics and Gynecology (M. Leboueuf, M. Lemyre), Faculty of Medicine, Laval University, Québec City, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Pouliot
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D015237:Dinoprost / Q000378:metabolism* / Q000494:pharmacology; D004715:Endometriosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D010532:Peritoneal Diseases / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D011982:Receptors, Prostaglandin; D042461:Vascular Endothelial Growth Factor A; C034671:prostaglandin F2alpha receptor; D015237:Dinoprost