Apoptosis and its pathway in early post-implantation embryos of diabetic rats.

It has been reported that diabetes-induced inappropriate apoptosis in embryos during neurulation may be one of the mechanisms leading to neural tube defects. We studied apoptosis and the apoptotic pathway occurring in early post-implantation period embryos of non-diabetic and streptozotocin (STZ)-induced diabetic rats. In quantitative RT-PCR, bax mRNA was constantly expressed to similar degree in embryos of non-diabetic and diabetic rats, while the expression of bcl-2 mRNA was significantly decreased in diabetic rat embryos compared to non-diabetic rat embryos. The increased number of terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-positive cells occurred selectively in the primitive brains of diabetic rat embryos compared to non-diabetic rat embryos. Immunohistochemical studies revealed that, in mirror sections, the staining of Bax and activated caspase-3 were observed in the TUNEL-positive cell area, but the expression of Bcl-2 in these apoptotic cells was generally too low to be detected. These results suggest that a Bax-regulated mitochondrial cytochrome c-mediated caspase-3 activation pathway might be involved in the diabetic embryopathy.