Maternal Factors in a Model of Type 1 Diabetes Differentially Affect the Development of Insulitis and Overt Diabetes in Offspring

Abstract

Type 1 diabetes, a multifactorial disease involving genetic and environmental factors, results from the destruction of pancreatic β-cells. The maternal environment has been suggested to be important in the development of diabetes. To assess the role of maternal factors in the development of insulitis and overt diabetes, we transplanted pre-implantation stage embryos of nonobese diabetic (NOD) mice, a model of type 1 diabetes, into the uterus of each recipient. Recipients were ICR and DBA/2J mice without diabetic genetic predisposition and NOD mice not exhibiting overt diabetes during the experiment; offspring were designated as NOD/ICR, NOD/DBA, and NOD/NOD, respectively; unmanipulated NOD offspring were also examined. NOD/ICR and NOD/DBA offspring developed insulitis significantly earlier than NOD/NOD offspring. However, overt diabetes was significantly suppressed in NOD/ICR and NOD/DBA offspring in comparison with NOD/NOD offspring. Insulin autoantibodies (IAAs) were undetectable in ICR and DBA/2J surrogate mothers and in NOD/ICR and NOD/DBA offspring at the onset of insulitis, suggesting that maternal factors other than transmitted IAAs induced the earlier onset. The present study indicates that altered maternal factors modify the immune response to islets, which in turn might affect the pathogenic course from insulitis to overt diabetes.