Acetaldehyde in vitro exposure and apoptosis: a possible mechanism of teratogenesis

Abstract 

Alcohol abuse by pregnant women can result in fetal alcohol effects (FAE) and fetal alcohol syndrome (FAS). Both ethanol itself and its main metabolite, acetaldehyde (Ach), are able to produce specific FAS-related malformations. In previous in vitro studies, we documented that 10-day-old rat embryos exposed to Ach show a characteristic embryonic Ach syndrome, histologically characterized by marked cellular death. As both necrosis and pathological apoptosis are teratological mechanisms, the aim of this work was to evaluate if cellular death, observed in Ach-exposed embryos, can be related to necrotic or apoptotic events. Ten-day-old rat embryos were cultured in the presence of Ach 30–60 μg/ml and stained with the vital dye acridine orange to visualize apoptotic areas. After fixation, the TUNEL [3′ terminal deoxynucleotide tranferase (TdT)-mediated dUTP-biotin nick end labeling] method was used to histologically identify apoptosis. Both acridine orange and TUNEL staining showed signs of physiological apoptosis in controls and abnormal apoptotic regions in Ach-exposed embryos. Our results show a clear correlation between malformed organs and apoptotic embryonic districts, suggesting the role of apoptosis in Ach-induced abnormalities.

Keywords: FAS, Malformations, Teratogenesis, Alcohol, Acetaldehyde, Apoptosis, Cellular death, Teratogenetic mechanisms