POSSIBLE ROLE FOR TNF-ALPHA IN EARLY EMBRYOPATHY ASSOCIATED WITH MATERNAL DIABETES IN THE RAT

Tumor necrosis factor (TNF) bioactivity was assessed in culture media conditioned with uterine cells collected from control or diabetic rats on days 5 and 8 of pregnancy, On both days, diabetic uterine cells re leased significantly more biologically active TNF than did control cel ls, and this activity was significantly decreased by the addition of a nti-TNF-alpha antibodies but not by the addition of normal IgG when WE HI 164 cells were used as a target, When uterine tissues from day 5 or day 8 pregnant dialjetic rats were tested by Northern blot analysis, TNF-alpha mRNAs were twofold more abundant than in control samples, bu t the difference was not statistically significant (P = 0.086 and 0.10 0, respectively), Immunohistochemical analysis of diabet;ic day 5 uter ine sections revealed that most of the TNF-alpha synthesis occurs in t he epithelium lining the uterine lumen. Finally, the growth of day-5 e mbryos in culture medium conditioned with day-5 diabetic uterine cells was significantly reduced when compared with that of embryos in mediu m conditioned with control cells. Embryonic development was markedly i mproved when anti-TNF-alpha antibodies were added to the diabetic-cell conditioned medium, Our data support the hypothesis that TNF-alpha ma y be implicated in the developmental deficiencies observed in preimpla ntation embryos from pregnant diabetic rats.