Transgenerational of Oxidative Damage Induced by Prenatal Ethanol Exposure on Spatial Learning/Memory and BDNF in the of Male Rats

Alcohol consumption during pregnancy harms fetal development, leading to various physical and behavioral issues. This study investigates how prenatal ethanol exposure triggers oxidative stress (OS) and affects neurotrophic factors (NTFs), particularly brain-derived growth factor (BDNF) gene expression in the hippocampus, influencing learning and memory decline across two generations of male offspring from ethanol-exposed female rats. A rat model of fetal alcohol spectrum disorder (FASD) was initially generated to reflect on the deficits in the first generation, and then those transmitted via the male germline to the unexposed male ones. The pregnant rats were thus divided into four groups, namely, the control group (CTRL) receiving only distilled water (DW), and three groups being exposed to ethanol (20 %, 4.5 g/kg) by oral gavage, during the first 10-day gestation (FG), the second 10-day gestation (SG), and the entire gestation (EG) periods. Subsequent Morris water maze (MWM) tests on male offspring revealed spatial learning deficits during the second and entire gestational periods in both generations. Analysis of antioxidant enzyme activity including glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA), and BDNF gene expression in the hippocampus further highlighted the impacts of prenatal ethanol exposure. The study results demonstrated that prenatal ethanol exposure caused spatial learning/memory deficits during the SG and EG, altered antioxidant enzyme activity, and reduced BDNF gene expression in both generations. The findings underscore the role of OS in developmental and behavioral issues in FASD rat models and suggest that lasting transgenerational effects in the second generation may stem from alcohol-induced changes.