title: Induction of epithelial cell apoptosis in the uterus by a mouse uterine ischemia-reperfusion model: possible involvement of tumor necrosis factor-alpha.
abstract: Menstruation in primates is preceded by a period of intense vasoconstriction, with resultant ischemia-reperfusion. Although apoptosis is involved in endometrial breakdown, the relationship between ischemia-reperfusion and apoptosis in the female genital tract has not been determined. To investigate the relationship between ischemia-reperfusion and apoptosis in the uterus, we analyzed a uterine ischemia-reperfusion model using BDF1 and C57BL/6 mice. Ischemia was induced by clamping the uterine horn and uterine artery for 5 to 30 min, followed by 6, 12, 24, or 48 h of reperfusion (n = 4 for each group). The number of TUNEL-positive endometrial cells increased with the duration of ischemia and reached a maximum at 24 h of reperfusion, but then tended to decrease at 48 h. Transmission electron micrographs of endometrial cells revealed a typical nuclear condensation, confirming the occurrence of apoptosis. The mRNA expression level of the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) in the uterus increased after reperfusion. Ischemia-reperfusion-induced endometrial apoptosis was markedly decreased in TNF-R p55-deficient mice, confirming the essential role of TNFalpha in the induction of apoptosis by ischemia-reperfusion (n = 4). Our results suggest that ischemia-reperfusion and subsequent TNFalpha expression may be critical factors in inducing endometrial cell apoptosis. Our mouse model could be suitable for investigating ischemia-related uterine injury in humans, particularly in menstruation.
authors.affiliation: IVF Namba Clinic, Osaka 550-0015 Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Okazaki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohno
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Shindo
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Ishimaru
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000172:deficiency / Q000235:genetics; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014599:Uterus / Q000098:blood supply* / Q000276:immunology / Q000293:injuries / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha