Fetuses of type 1 and type 2 diabetic women experience higher incidences of malformations and fetal death as compared to non diabetics even when they achieve adequate glycemic control during the first trimester. We hypothesize that maternal diabetes adversely affects the earliest embryonic stage post fertilization and programs the fetus to experience these complications.

To test this hypothesis we transferred either one-cell mouse zygotes or blastocysts from either streptozotocin-induced diabetic or control mice into non-diabetic pseudopregnant female recipients. We then evaluated the fetuses at embryonic day 14.5 in order to assess fetal growth and the presence or absence of malformations. We found that fetuses from the diabetic mice transferred at the blastocyst stage but also as early as the one-cell zygote stage displayed significantly higher rates of malformations consistent with neural tube closure problems and abdominal wall and limb deformities. In addition, both these groups of fetuses were significantly growth retarded. In order to determine if this phenomenon was due to high glucose concentrations, two-cell embryos were cultured to a blastocyst stage in 52mM D-glucose or L-glucose as an osmotic control, transferred into non-diabetic pseudopregnant mice, and examined at embryonic day 14.5. These embryos did not demonstrate any evidence of malformations, how ever did experience significantly higher rates of resorptions, lower implantation rates and they were significantly smaller at e14.5. In summary, exposure to maternal diabetes during oogenesis, fertilization and the first 24 hours was enough to program permanently the fetus to develop significant morphologic changes.