While some fathers planning a family may be left in a bivalent state when deciding about smoking cannabis or nicotine, new research has cleared the air. THC and nicotine both prime an autism spectrum disorder profile in sperm through altering DNA methylation within bivalent chromatin states.
In their seminal paper, researchers from the lab of Susan Murphy at Duke University reported on lower sperm concentration and genes with altered DNA methylation in both humans and rats following THC exposure. Since many genes involved in development tend to be located in bivalent chromatin marked by both activating (H3K4me3) and repressive (H3K27me3) histone post-translational modifications, the team hypothesized in their latest report that bivalent status may make genes more vulnerable to environmental exposures like THC and nicotine. To test their hypothesis, the researchers exposed rats to THC or saline in different ways to assess the resulting sperm methylome via reduced representation bisulfite sequencing (RRBS) and pyrosequencing.
Here’s what they found:
- THC induces DNA methylation changes at neurodevelopmental genes in sperm when orally administered or injected
- Nicotine via osmotic pump also induces sperm DNA methylation changes at neurodevelopmental genes
- Seven autism spectrum disorder candidate genes are impacted by some or all these exposures
- By using publicly available data, they found significant overlaps between:
- Autism candidate genes and bivalent chromatin
- Their list of differentially methylated genes in human sperm from cannabis users and bivalent chromatin
Taken together, these findings suggest that being located in bivalent chromatin makes genes more vulnerable to environmental exposures, and ultimately poised for disrupted DNA methylation. So, if you’re a father planning a family, it’s best to modify your perspective with H3K27me3 and avoid THC and/or nicotine consumption in order to prime your child for their best possible outcome.
Check out this hazy shade of bivalent chromatin over at Scientific Reports, September 2020.