Mothers who drink during pregnancy expose their developing babies to ethanol, and excessive drinking often produces devastating birth defects collectively termed fetal alcohol spectrum disorder (FASD). These defects include craniofacial defects, cognitive impairment, sensorimotor disabilities and organ deformities, including various congenital heart defects (CHDs), particularly septal and conotruncal defects. Genesis mechanisms for FASD-associated CHDs are not well understood.
Using a zebrafish model, experiments tested whether alcohol interferes with different heart development events or the multiple cardiac precursors that may contribute to CHD genesis.
These experiments showed that ethanol affects various cardiac regulatory networks in multiple steps of cardiogenesis (specification, myocardial migration, differentiation, looping, chamber morphogenesis, and endocardial cushion formation). Retinoic acid and folic acid co-treatment with ethanol had differential rescue effects on FASD-induced cardiac defects. Early (first heart field) and late-added (second heart field and cardiac neural crest precursors) cardiac precursors were reduced by ethanol exposure. Experiments showed dysregulation of BMP, Notch and other signaling pathways during atrioventricular valve formation produced persistent valve defects.
Together, these results show that embryonic ethanol exposure disrupts critical cardiac morphogenic events and reduce cardiac precursor contributions to the growing heart. Additional mechanistic studies are needed to identify key events that can be targeted therapeutically.