Acute alcohol exposure induces reproductive behavior defects, subfertility, brain transcriptomic changes of parental zebrafish and malformation in their offspring.

Alcohol is a prevalent addictive substance and the consequences of alcohol abuse pose a significant public health concern. Despite its prevalence and pervasiveness in the modern world, the underlying mechanisms mediating alcohol's deleterious effects on vertebrate reproductive behaviors remain poorly understood due to its complex pharmacology. Using adult zebrafish (Danio rerio) as a model, we investigated the effects of 40-minute acute alcohol exposure (0.25%, 0.50%, 0.75% vol/vol) on reproductive behaviors, fecundity, offspring development, and brain transcriptomes. Results show that acute alcohol exposure impairs courtship behaviors in a dose-dependent manner, along with significantly suppressed fecundity at 0.75% alcohol group. Additionally, parental exposure also induces offspring deformities and growth retardation. The brain transcriptomic analysis shows that 127 co-upregulated genes and 113 co-downregulated genes in female brain, 58 co-upregulated genes and 91 co-downregulated genes in male brain; GO/KEGG analyse further reveal the key signaling pathways and genes involved in alcohol-induced reproductive impairment, with sexually dimorphic transcriptomic patterns observed in the brains of male and female zebrafish. This study demonstrates that acute alcohol exposure of parental zebrafish can influence brain function, courtship behavior, and offspring development, providing insights into the reproductive toxicity of alcohol.