TNFalpha in the pathogenesis of diabetes-induced embryopathies: Functions and targets

Arkady Torchinsky*, Vladimir Toder

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Hyperglycemia-induced increase in the production of reactive oxygen species (ROS) is proposed to be an initial step in the pathogenesis of diabetes-induced spontaneous abortions and structural inborn anomalies. However, the subsequent steps in this process are incompletely understood. One of the key molecules involved is tumor necrosis factor-alpha (TNFα): its expression is regulated by ROS and it regulates ROS production in turn. This cytokine has been the focus of many studies addressing the mechanisms of different forms of diabetes-induced embryopathies, such as early pregnancy loss, inborn anomalies, fetal growth retardation as well as some pathologies appearing during adult life. In this review, we analyze the results of these studies and discuss how TNFα may regulate the response of pre- and post-implantation stage embryos to diabetes-induced detrimental stimuli. The data presented in this review suggest that TNFα may play a dual role in the pathogenesis of diabetes-induced embryopathies. It may act both as a mediator of diabetes-induced embryotoxic stimuli leading to the death of peri-implantation stage embryos and, possibly, as a suppressor of diabetes-induced apoptosis in post-implantation stage embryos. It also appears that TNFα fulfills these functions via interaction with leukemia inhibitory factor (LIF) and the transcription factor NF-κB. These molecules are presently considered as attractive targets for the treatment of diabetes-induced complications. Therefore, further studies addressing their role in the mechanisms underlying diabetes-induced embryopathies are needed to evaluate the safety of such therapies for diabetic women of childbearing age.

Original languageEnglish
Pages (from-to)200-208
Number of pages9
JournalReview of Diabetic Studies
Volume4
Issue number4
DOIs
StatePublished - 2007

Keywords

  • Diabetes
  • Embryopathy
  • Inborn anomalies
  • LIF
  • NF-kappaB
  • Pregnancy loss
  • TNFalpha

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