title: Omega-3 polyunsaturated Fatty acids suppress the cystic lesion formation of peritoneal endometriosis in transgenic mouse models.
abstract: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Tomio
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.forename: Ayumi
authors.initials: A
authors.lastname: Taguchi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Isobe
authors.forename: Ryo
authors.initials: R
authors.lastname: Iwamoto
authors.forename: Aki
authors.initials: A
authors.lastname: Yamashita
authors.forename: Satoko
authors.initials: S
authors.lastname: Kojima
authors.forename: Mayuyo
authors.initials: M
authors.lastname: Mori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagamatsu
authors.forename: Takahide
authors.initials: T
authors.lastname: Arimoto
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Oda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Makoto
authors.initials: M
authors.lastname: Arita
authors.forename: Shiro
authors.initials: S
authors.lastname: Kozuma
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010532:Peritoneal Diseases / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C475064:12-15-lipoxygenase; D015525:Fatty Acids, Omega-3; D015850:Interleukin-6; D012333:RNA, Messenger; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase
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