Insulin-dependent (type 1) diabetes is an auto-immune disorder that produce
s secondary complications in numerous non-immunological systems. Changes in
the synthesis and action pattern of several cytokines have been associated
with the development of these alterations. Based on the clinical facts tha
t the pregnant and non-pregnant functions of the reproductive system are al
so disrupted by diabetes, our laboratory has decided to concentrate its res
earch activities on the hypothesis that cytokines may be implicated in the
uteropathy and embryopathy associated with the metabolic disorder. This rev
iew article summarizes our major findings concerning the synthesis of TNF-a
lpha and IL-1 beta in the uterus of diabetic rats, and in cultures of roden
t uterine cells upon their exposure to high concentrations of glucose. The
paper also reviews evidence that both the peri-implanting embryo and the ep
ithelial cell layer lining the uterine lumen are targets for the deleteriou
s influence of excess TNF-alpha. If confirmed in the uterus of diabetic pat
ients, these observations may explain how cytokines contribute to the dysre
gulation of crucial reproductive events like menstruation and embryo implan
tation in humans.