Expression of Tumor Necrosis Factor-α in the Pregnant Uterus of Diabetic Mice: Effect of Maternal Immunopotentiation


  • A. Fein,

  • E. Kostina,

  • S. Savion,

  • H. Orenstein,

  • J. Shepshelovich,

  • A. Torchinsky,

  • V. Toder,

  • A. Ornoy

Address reprint requests to Amos Fein, Department of Embryology and Teratology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69778, Israel.



PROBLEM: Tumor necrosis factor (TNF)-α mRNA and protein are expressed in the pregnant uterus of streptozotocin-induced diabetic mice at various stages of pregnancy. We intend to characterize their pattern and to evaluate whether the potentiation of the maternal immune system alters the pattern of the expression of the cytokine.
METHOD OF STUDY: Diabetes was induced in ICR mice by streptozotocin injection. To modulate maternal immune responses, ICR mice were injected intrauterine with rat splenocytes 3 weeks before mating. The expression of TNF-α mRNA and protein was evaluated by in situ hybridization and immunohistochemistry techniques.
RESULTS. The population of diabetic mice used in this study demonstrated a reduction in pregnancy rate and an increased number of litters with severely malformed fetuses. It has been observed that these disturbances are associated with a clear increase in TNF-α mRNA and protein expression in the uterus of these mice. Maternal immunopotentiation, while improving reproductive performance of these diabetic mice, was found to be accompanied by a reduced expression of TNF-α, both at the mRNA and protein level.
CONCLUSIONS. The results of the present study suggest a possible involvement of TNF-α in mechanisms underlying diabetes-associated dismorphogenesis. Normalization of TNF-α expression by maternal immunopotentiation might represent a mechanism mediating its protective effect against diabetes-induced embryotoxic insult.