Optical coherence angiography to assess the dose-effect relationship of prenatal alcohol exposure on fetal brain vasculature

Abstract

Prenatal alcohol exposure (PAE) is a leading cause of developmental disabilities worldwide and thus, is one of the best-known causes of preventable birth defects. Its effects can persist throughout life as physical and cognitive growth and development deficits. Previous studies have demonstrated that the acute effects of prenatal alcohol exposure on fetal brain vasculature diminish brain growth and decrease cerebrovascular blood flow. In this study, we use correlation mapping optical coherence angiography to assess the dose-effect relationship of prenatal alcohol exposure on fetal brain vasculature in utero in a mouse model (C57BL/6J). We evaluated multiple alcohol dosages (1.5 g/kg, 3.0 g/kg, and 4.5 g/kg) at gestational day (GD) 14.5 followed immediately by imaging at GD 14.5. We also studied multiple dosing effects by administering ethanol via intragastric gavage at GD 12.5, 13.5, and 14.5 for each dose (1.5 g/kg, 3.0 g/kg, and 4.5 g/kg) followed by imaging at GD 14.5. Results show vasoconstriction of the main imaged blood vessel after dosing for three consecutive days. When the embryo was exposed to the lowest dose, 1.5 g/kg of ethanol, there was a greater decrease in the main blood vessel diameter, compared to the highest dose, 4.5 g/kg of ethanol. For the acute dosing studies, where a single ethanol dose was administered at GD 14.5, the results show a higher percentage change in vessel diameter over time for 4.5 g/kg, which was the highest dose, but with a higher initial percentage change at a lower dose. The multiple dose and single dose exposure to ethanol results demonstrated significant changes in fetal brain vasculature. Multiple dosing of prenatal alcohol exposure shows a significant effect in the vasculature for each dosage, demonstrating the dose-effect relationship of multiple ethanol exposure on embryo brain vasculature compared to a single dose exposure.