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

Congenital malformations are the leading cause of perinatal death among infants of diabetic women. Abnormal fuel metabolism and hyperglycemia have been shown to disturb embryogenesis during the earliest pre- and postimplantation stages in mice. This review presents a new model to explain, in part, adverse pregnancy outcomes associated with diabetes. In this model, by altering gene expression in developing tissues, raised glucose concentrations led to premature programmed cell death in key progenitor cells of the mouse blastocyst or in emerging organ structures in the mouse postimplantation embryo, resulting in abnormal morphogenesis or miscarriage. Although recent studies 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 findings are also applicable to human pregnancy.