While some compound effects, like interest, are desired, there are others we should avoid. While we know that stress and alcohol have adverse effects on pregnancy that can be reflected epigenetically, it turns out that the combination of the two can have distinct detrimental effects.
Previously, the lab of Shiva Singh at Western University (Ontario, Canada) has studied patient samples and developed several mouse models of Fetal Alcohol Spectrum Disorders (FASD). They’ve found DNA methylation changes in both organisms, as well as histone modification and non-coding RNA changes in the mice. It’s clear that epigenetic changes occur in FASD; how these changes interact with the numerous environmental factors in the disorder is an interesting and under-researched area. Early life stress increases the risk of negative behavioral outcomes in FASD. Dr. Singh’s group examined this compound effect by giving mice either ethanol or water (control) in utero via maternal consumption, then either intermittent maternal separation or normal rearing after birth to model an early life stress. They wanted to examine how these different conditions affected DNA methylation (MeDIP-seq) and the transcriptome (RNA-seq) in the hippocampus (important for learning and memory) of the resultant pups. Here’s what they found:
- Early life stress and prenatal ethanol exposure result in different changes in DNA methylation at different gene promoters
- 1264 genes in the ethanol group, 1472 in the stress group, 958 in the stress+ethanol group, with 120 genes shared across the three groups
- Prenatal ethanol exposure affected DNA methylation at genes involved in transcriptional regulation, maternal separation affected histone regulatory genes and immune genes, and the combination of stress+ethanol affected neurodevelopmental and immune genes
- There was little overlap between DNA methylation changes and gene expression changes in the same mice, although the common genes are involved in histone methylation and neurological processes
- This disparity is consistent with other studies in FASD and other disorders and suggests that DNA methylation reflects past, present, and future events, while the transcriptome may require other stimulating conditions to make the expression alterations apparent
This study shows that the combination of prenatal ethanol exposure and early life stress has a distinct effect compared to either exposure alone. Lead author Bonnie Alberry shares: “We found a disparity between the transcriptome and promoter DNA methylation in our FASD model, indicating that more must be done to understand how long-term changes in the brain are maintained. The ability of the brain epigenome to respond to early life environment gives us hope that there’s room for intervention after an FASD diagnosis, what happens after the initial prenatal ethanol exposure matters.”
Get all the compound details in Frontiers in Genetics, February 2020