title: Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.
abstract: Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.
authors.affiliation: Endocrinologie de la Reproduction, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
authors.forename: Halima
authors.initials: H
authors.lastname: Rakhila
authors.affiliation: Département d'obstétrique et gynécologie, Faculté de médecine de l'Université Laval, Québec, Québec, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Girard
authors.affiliation: Département d'obstétrique et gynécologie, Faculté de médecine de l'Université Laval, Québec, Québec, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Leboeuf
authors.affiliation: Département d'obstétrique et gynécologie, Faculté de médecine de l'Université Laval, Québec, Québec, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Lemyre
authors.affiliation: Endocrinologie de la Reproduction, Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada; Département d'obstétrique et gynécologie, Faculté de médecine de l'Université Laval, Québec, Québec, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Akoum
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017931:DNA Primers; D004715:Endometriosis / Q000503:physiopathology*; D004717:Endometrium / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D006652:Histological Techniques; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010537:Peritoneum / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse