The aim of this study was to determine the possible fetal effects of interaction between maternal diabetes and acute doses of alcohol. Pregnant TO mice were made diabetic by a single injection of
streptozotocin (STZ) on gestation day (GD) 2. Single dose of 0.003 or 0.03 ml/g
body weight of fresh
ethanol (25% v/v of
absolute alcohol in
normal saline) was injected into groups of diabetic and nondiabetic animals on
GD 7 or 8. One group of diabetic animals had a daily dose of 6-8 IU of
insulin subcutaneously. Fetuses were collected on GD 18. There was a significant increase in the incidence of implantation failure in the diabetes plus
ethanol groups and
insulin control group.
Ethanol injection on
GD 7 accentuated diabetes-related embryonic resorption and
intrauterine growth retardation (IUGR). This effect was less marked in the diabetic group treated with
ethanol on GD 8. Diabetes alone produced a greater incidence of IUGR than
ethanol alone. Midfacial hypoplasia and minor anomalies were found more frequently in the combination treatment groups.
Holoprosencephaly and thymus hypoplasia observed in diabetic groups were found to be reduced in frequency in the diabetes plus
ethanol groups, suggesting an antagonistic type of
ethanol-diabetes interaction, stage-dependently. Since severely malformed embryos are known to be resorbed/killed in utero in mice, this reduction might reflect the magnitude of early death of severely malformed embryos. These data suggest that the interaction effects are possibly related to alterations in fundamental developmental processes of early embryos.