TNF-α in Pregnancy Loss and Embryo Maldevelopment: A Mediator of Detrimental Stimuli or a Protector of the Fetoplacental Unit?

摘要

>Purpose>: Tumor necrosis factor alpha (TNF-α), a multifunctional cytokine, has been identified in the ovary, oviduct, uterus, and placenta, and is expressed in embryonic tissues. For many years TNF-α was mainly considered to be a cytokine involved in triggering immunological pregnancy loss and as a mediator of various embryopathic stresses. However, data collected during the last decade has characterized TNF-α not only as a powerful activator of apoptotic, but also antiapoptotic signaling cascades, as well as revealed its regulatory role in cell proliferation. This review summarizes and conceptualizes the studies addressing TNF-α-activated intracellular signaling and the possible functional role of TNF-α in embryonic development.>Methods>: Studies addressing the role of TNF-α in intercellular signaling, in vivo studies addressing the functional role TNF-α in spontaneous and induced pregnancy loss, and studies addressing the role of TNF-α in fetal malformations were reviewed. Comparative studies in TNF-α knockout and TNF-α positive mice were performed to evaluate embryonic death, structural anomalies in fetuses, the degree of apoptosis and cell proliferation, and the activity of molecules such as caspases 3 and 8, the NF-κB, (RelA), IκBα in some target embryonic organs shortly after exposure to embryopathic stresses.>Results>: It is proposed that the possible essential function of TNF-α may be to prevent the birth of offspring with structural anomalies.>Conclusions>: TNF-α will boost death signaling to kill the embryo if initial events (damages) triggered by detrimental stimuli may culminate in structural anomalies, and stimulate protective mechanisms if the repair of these damages may prevent maldevelopment.