IMMUNOSTIMULATION INCREASES THE RESISTANCE OF MOUSE EMBRYOS TO THE TERATOGENIC EFFECT OF DIABETES-MELLITUS

The present work was aimed to assess the possible effect of stimulatio n of the maternal immune system on the teratogenic potential of diabet es mellitus. ICR female mice were immunized with splenocytes of male r ats 3 weeks before the beginning of mating and were injected with 240 mg/kg streptozocin (STZ) 10 days after immunization. Females with bloo d glucose levels over 27.8 mmol/l and HbA(1c) levels over 6 standard d eviations (SD) above the mean of intact animals were used for teratolo gical studies. The rate of malformed fetuses, resorptions and fetal we ights were evaluated for animals killed on day 19 of pregnancy using r outine teratological methods. Also, phenotyping of spleen cells of the se females was performed by fluorescein activated cell sorter analysis . Two main effects possibly due to immunostimulation of ICR females we re observed: 1) immunostimulated females had significantly fewer litte rs with malformed fetuses than non-immunized females: only 4 litters o ut of 22 (18%) compared to 10 out of 16 (63 %). Correspondingly, the i ncidence of malformed fetuses was also decreased: 2.1 compared to 8.9 %; 2) a significant increase in the pregnancy rate in immunized diabet ic ICR mice: 69 % as compared to 44 % in non-immunized diabetic female s. Also, immunostimulation resulted in a visible increase in spleen ce llularity and a certain increase in the number of cells with mature T- cell and macrophage surface markers. These results strongly suggest th at immunostimulation increases the tolerance of ICR females to the ter atogenic effect of STZ-induced diabetes.