Sex‐dependent responses to high concentration of binge ethanol in spleen of adolescent F344 rats

Background We previously reported that binge ethanol induces atrophy of the spleen, a key immune organ, in adolescent male F344 rats. Because there are significant sex effects in immune function, we investigated whether binge ethanol exerts sex‐dependent effects on the spleen, including producing splenic atrophy. Methods We gave F344 rats ethanol (4.8 g/kg/day; 52% w/v; i.g.) on postnatal days [PND] 36 ~ 38 and sacrificed them on PND 39 for spleen collection. We performed immunophenotyping analysis of splenic cells and examined the expression of 158 genes related to alcohol metabolism, epigenetic modification, and immune regulation in the spleens of adolescent (PND 39) male and female rats. Results Following a 3‐day ethanol exposure, a loss of body weight, and absolute and relative spleen weight, was seen only in male adolescent rats. Ethanol altered the relative proportions of lymphocyte subtypes in both sexes with different patterns. We also found that 3‐day ethanol exposure induced sex‐dependent gene expression changes in spleen. Among the 158 genes studied, the expression of only three genes was significantly increased in female rats. However, the expression of 30 genes was significantly increased/decreased in male rats. Female rats had greater expression of alcohol metabolizing enzyme genes in the spleen under physiological conditions and when stimulated by binge ethanol. The genes are involved in epigenetic modification were differentially expressed in a sex‐dependent manner. Conclusion We found that male adolescent rats were more sensitive to binge ethanol than female rats. Differential expression of the genes related to alcohol metabolism and epigenetic modification (of DNA methyltransferase and histone deacetylases) between the sexes could account for the observed sex‐dependent responses to binge ethanol in adolescent rats. Male adolescent F344 rats are more sensitive to binge alcohol than female rats. Following 3‐day binge alcohol administration, a loss in body weight, absolute and relative spleen weight occurred only in male rats. Alcohol altered the relative proportions of lymphocyte subtypes in both sexes with different patterns, and induced sex‐dependent spleen gene expression changes. Differential expression of genes related to alcohol metabolism and epigenetic modification between two genders may account for sex‐dependent responses to binge alcohol in adolescent rats.