Sex-Specific Effects of Early Acute Prenatal Alcohol Exposure and Mild Juvenile Stress on the Risk of Developing Type 2 Diabetes Mellitus and Liver Abnormalities in Mice

Emerging evidence indicates that early acute prenatal alcohol exposure (PAE) and mild childhood stress may be more widespread and harmful than previously thought, redirecting attention from chronic and severe insults. This study employs a mouse model to evaluate the individual and combined effects of early acute PAE and mild juvenile stress on type 2 diabetes mellitus (T2DM) risk and liver health. Pregnant dams were administered water or ethanol during gastrulation, followed by exposure to daily handling or mild stress from postnatal days 28–56. T2DM risk was evaluated using glucose and insulin measures, while liver health was assessed through size and expression changes. A sexually dimorphic effect emerged: females demonstrated increased T2DM risk, whereas males exhibited liver abnormalities. Both PAE and stress contributed to metabolic impairments, with their combination exacerbating certain outcomes. Overall, this study offers a model for investigating under-recognized early-life insults and their long-term metabolic impacts.