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BOR - Papers in Press, published online ahead of print January 26, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.035840
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BIOLOGY OF REPRODUCTION 72, 1282–1288 (2005)
DOI: 10.1095/biolreprod.104.035840
© 2005 by the Society for the Study of Reproduction, Inc.

Induction of Epithelial Cell Apoptosis in the Uterus by a Mouse Uterine Ischemia-Reperfusion Model: Possible Involvement of Tumor Necrosis Factor-{alpha}

Mitsuo Okazaki 2,3, Toshifumi Matsuyama 1 3, Tomoko Kohno 3, Hisakazu Shindo 3, Takehiko Koji 4, Yoshiharu Morimoto 2, and Tadayuki Ishimaru 5

IVF Namba Clinic,2 Osaka 550-0015 Japan Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology,3 Department of Histology and Cell Biology,4 Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 Japan Department of Obstetrics and Gynecology,5 Nagasaki University School of Medicine, Nagasaki 852-8501, Japan

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 (TNF{alpha}) 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 TNF{alpha} in the induction of apoptosis by ischemia-reperfusion (n = 4). Our results suggest that ischemia-reperfusion and subsequent TNF{alpha} 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.

apoptosis, cytokines, menstrual cycle, uterus


1 Correspondence: Toshifumi Matsuyama, Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. FAX: 81 95 849 7083;tosim{at}net.nagasaki-u.ac.jp




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[Abstract] [Full Text] [PDF]




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