Poorly controlled maternal diabetes has an adverse effect on methylation of the maternal imprinting gene Peg3, contributing to impaired development in offspring, shows researchers.
Previous studies have revealed that offspring of diabetic mothers display a higher incidence of malformations and fetal death, even when a one-cell embryo is transplanted from a diabetic to a non-diabetic mother. Diabetic mothers' oocytes tend to exhibit reduced glucose metabolism, compromised communication between cumulus cells and oocytes, mitochondrial malfunction, and a decreased ovulation rate, all of which can be traced back to reduced gene expression in the embryos.
Qing-Yuan Sun and Zhao-Jia Ge of the Chinese Academy of Sciences hypothesized that the reduced gene expression results from disturbed DNA re-methylation during oogenesis and oocyte maturation. The team bred and examined three different mouse populations: one with spontaneously occurring diabetes, one with diabetes induced by STZ injection, and one without diabetes. After mating on Day 15, the diabetic mice presented with reduced pregnancy rates (approx. 74% vs. 100% in non-diabetic mice) and increased embryo death rates (approx. 16% vs. 0%), consistent with previous reports.
As for the female offspring of diabetic mothers, their oocytes did not appear to have any methylation abnormalities; however, due to the difficulty of producing offspring conceived after Day 15, it will be extremely difficult to determine whether those females are similarly unaffected.