TNF-alpha-mediated stress-induced early pregnancy loss: a possible role of leukemia inhibitory factor.
BACKGROUND
Leukemia inhibitory factor (LIF) is at present suggested to be essential for implantation in mammals. In parallel, the possibility that it may also be involved in the pathogenesis of stress-induced early embryonic death seems to emerge from studies, which addressed the embryotoxic potential of another cytokine, tumor necrosis factor-alpha (TNF-alpha). In this brief review, we discuss this possibility based on these studies as well as on those addressing TNF-alpha and LIF signaling.


METHODS
Existing data were reviewed critically.


RESULTS
Data summarized in this review suggest that: (1) TNF-alpha may act as a mediator of stress-induced early embryonic death, (2) TNF-alpha-mediated early embryonic death induced by some detrimental stimuli may be attributed to a dysfunction of mechanisms, which are critical for the ability of the uterus to become receptive to blastocysts, allowing implantation, (3) one such mechanism was shown to be associated with LIF signaling in uterine cells, and (4) TNF-alpha seems to have the potential to affect LIF signaling.


CONCLUSIONS
Data presented in the this review suggest LIF as a good candidate for further studies addressing molecular mechanisms underlying stress-induced early embryonic death.
Torchinsky
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Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Markert
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Toder
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D000818:Animals; D001755:Blastocyst / Q000276:immunology; D005260:Female; D005313:Fetal Death / Q000209:etiology* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D053605:Leukemia Inhibitory Factor; D051379:Mice; D011247:Pregnancy; D015398:Signal Transduction; D013312:Stress, Physiological / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014599:Uterus / Q000276:immunology
D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D014409:Tumor Necrosis Factor-alpha