Epigenetic insight of prenatal alcohol exposure on stress axis development: Systematic review with meta-analysis approaches.

In this systematic review with elements of meta-analytic approaches we employed publicly available Gene Expression Omnibus (GEO) datasets to determine the role of epigenetic mechanisms in prenatal alcohol exposure (PAE)-induced dysfunction of hypothalamic-pituitary-adrenal (HPA) axis functions in the offspring. Several studies have demonstrated that PAE has long-term consequences on HPA axis functions in the offspring. Reports of some of these studies determined that alcohol-induced epigenetic alterations during fetal development persist in adulthood. However, additional research is necessary to understand the major epigenetic events leading to alcohol-induced teratogenesis on the HPA axis. Our network analysis of GEO datasets identified key pathways in relevance to alcohol-mediated histone modifications, DNA methylation and miRNA involvement associated with PAE-induced alteration of the HPA axis. Our analysis indicated that PAE perturbated the epigenetic machinery to activate corticotrophin-releasing hormone, while it suppressed opioid, glucocorticoid receptors, and circadian clock genes. We hope that our results would be helpful to further understanding and investigating the epigenetic basis of alcohol effect on the HPA axis development.