Hyperglycemia and apoptosis: mechanisms for congenital malformations and pregnancy loss in diabetic women

Congenital malformations are the leading cause of perinatal death among inf ants of diabetic women. Abnormal fuel metabolism and hyperglycemia have bee n shown to disturb embryogenesis during the earliest pre- and postimplantat ion stages in mice. This review presents a new model to explain, in part, a dverse pregnancy outcomes associated with diabetes. In this model, by alter ing gene expression in developing tissues, raised glucose concentrations le d to premature programmed cell death in key progenitor cells of the mouse b lastocyst or in emerging organ structures in the mouse postimplantation emb ryo, resulting in abnormal morphogenesis or miscarriage. Although recent st udies are still somewhat speculative and have currently only been explored in the mouse,this paradigm is supported by examples in other cell systems, which include human-derived cell lines, thereby suggesting that these findi ngs are also applicable to human pregnancy.