Expression of tumor necrosis factor-alpha in the pregnant uterus of diabetic mice: Effect of maternal immunopotentiation

PROBLEM: Tumor necrosis factor (TNF)-alpha mRNA and protein are expressed i n the pregnant uterus of streptozotocin-induced diabetic mice at various st ages of pregnancy. We intend to characterize their pattern and to evaluate whether the potentiation of the maternal immune system alters the pattern o f the expression of the cytokine. METHOD OF STUDY: Diabetes was induced in ICR mice by streptozotocin injecti on. To modulate maternal immune responses, ICR mice were injected intrauter ine with rat splenocytes 3 weeks before mating. The expression of TNF-alpha mRNA and protein was evaluated by in situ hybridization and immunohistoche mistry techniques. RESULTS. The population of diabetic mice used in this study demonstrated a reduction in pregnancy rate and an increased number of litters with severel y malformed fetuses. It has been observed that these disturbances are assoc iated with a clear increase in TNF-alpha mRNA and protein expression in the uterus of these mice. Maternal immunopotentiation, while improving reprodu ctive performance of these diabetic mice, was found to be accompanied by a reduced expression of TNF-alpha both at the mRNA and protein level. CONCLUSIONS. The results of the present study suggest a possible involvemen t of TNF-alpha in mechanisms underlying diabetes-associated dismorphogenesi s. Normalization of TNF-alpha expression by maternal immunopotentiation mig ht represent a mechanism mediating its protective effect against diabetes-i nduced embryotoxic insult.