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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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Mitsuo Okazaki
Toshifumi Matsuyama
Yoshiharu Morimoto
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Submitted September 2, 2004
Returned for revision September 28, 2004
Accepted January 20, 2005

Immunology


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

Mitsuo Okazaki , Toshifumi Matsuyama *, Tomoko Kohno , Hisakazu Shindo , Takehiko Koji , Yoshiharu Morimoto , and Tadayuki Ishimaru

* To whom correspondence should be addressed. E-mail: tosim{at}net.nagasaki-u.ac.jp.

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. In order 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 the typical nuclear condensation, confirming the occurrence of apoptosis. The mRNA expression level of the proinflammatory cytokine, 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 to induce endometrial cell apoptosis. Our mouse model could be suitable for investigating ischemia-related uterine injury in humans, particularly in menstruation.

Key words: Apoptosis • Cytokines • Menstrual cycle • Uterus


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E.A. Campbell, L. O'Hara, R.D. Catalano, A.M. Sharkey, T.C. Freeman, and M. H. Johnson
Temporal expression profiling of the uterine luminal epithelium of the pseudo-pregnant mouse suggests receptivity to the fertilized egg is associated with complex transcriptional changes
Hum. Reprod., October 1, 2006; 21(10): 2495 - 2513.
[Abstract] [Full Text] [PDF]


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