TNF-α-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-α (TNF-α). In this brief review, we discuss this possibility based on these studies as well as on those addressing TNF-α and LIF signaling. Methods: Existing data were reviewed critically. Results: Data summarized in this review suggest that: (1) TNF-α may act as a mediator of stress-induced early embryonic death, (2) TNF-α-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-α seems to have the potential to affect LIF signaling. Conclusion: Data presented in the this review suggest LIF as a good candidate for further studies addressing molecular mechanisms underlying stress-induced early embryonic death.