Maternal diabetes increases apoptosis in mice oocytes, not 2-cell embryos.

Apoptosis may be closely involved in diabetes-induced embryonic malformations. We aimed to investigate the occurrence of apoptosis at an early stage of development, in oocytes and 2-cell embryos of streptozotocin-induced diabetic mice and nondiabetic mice. Diabetic mouse ovarian sections stained with hematoxylin and eosin showed reduced number of growing follicles and delayed oocyte development. Annexin V-positive oocytes were higher in number in diabetic mice than in nondiabetic mice. Quantitative RT-PCR and immunofluorescence analysis revealed the expression of Bax and caspase-3 significantly higher in diabetic than nondiabetic oocytes. In contrast, 2-cell embryos of diabetic and nondiabetic mice showed no annexin V-positive staining. Bax expression was elevated in diabetic 2-cell embryos, but caspase-3 expression did not significantly differ between diabetic and nondiabetic 2-cell embryos. Electron microscopy revealed increased number of swollen mitochondria in diabetic 2-cell embryos. These results suggested that maternal diabetes might increase oocyte apoptosis by a Bax-caspase-3 pathway to play a role in embryonic malformations by delayed oocyte development. Development of 2-cell embryos might be adversely affected by maternal diabetes, but not through Bax-regulated caspase-3 apoptotic pathway.