Cannabis use was associated with widespread hypomethylation of the autism-linked gene DLGAP2 in human sperm, and similar changes were found in rat sperm after THC exposure and in the brains of offspring from THC-exposed fathers.
Autism researchers, reproductive epigeneticists, and men using cannabis who plan to have children.
Autism gene DLGAP2 hypomethylated in human sperm of cannabis users; changes found in rat offspring brains
What the researchers found
Using RRBS, cannabis use was associated with significant hypomethylation of the autism-linked gene DLGAP2 in human sperm. Targeted analysis confirmed differential methylation at 9 CpG sites in intron 7. DLGAP2 methylation and expression in human fetal brain tissue were inversely correlated. THC exposure in rats produced similar methylation changes in sperm, and these changes were also found in the nucleus accumbens of offspring from THC-exposed fathers.
Why it matters
This is the first demonstration of a specific gene (DLGAP2) where cannabis-associated sperm methylation changes may transmit to offspring brain tissue via the father. DLGAP2 is strongly implicated in autism and synaptic function.
The numbers in context
DLGAP2 hypomethylated in human sperm of cannabis users; 9 CpG sites in intron 7; methylation-expression inversely correlated in fetal brain; similar changes in rat sperm after THC; changes present in offspring nucleus accumbens.
How the study worked
RRBS of human sperm from cannabis users vs non-users, with pyrosequencing validation at DLGAP2. Cross-species validation in THC-exposed rats. DLGAP2 methylation-expression correlation in human conceptal brain tissue. Offspring brain analysis in rat model.
What this study cannot tell us
Human sperm data is cross-sectional (cannot prove causation); small human samples; rat model used different THC route than human smoking; offspring changes found in only one brain region; does not assess autism-related behavior in offspring.
How to read the evidence
Moderate: cross-species validation (human and rat) with mechanistic plausibility, but cross-sectional human data.
When this study was published
Published 2020.
The bigger picture
If paternal cannabis use alters epigenetic marks at autism-related genes and these marks transmit to offspring brains, it would represent a novel environmental risk factor for neurodevelopmental disorders mediated through the father.
Questions still open
- Does paternal cannabis use increase autism risk in children? Can these epigenetic changes be reversed by cannabis cessation before conception?
Common questions
Could a father cannabis use contribute to autism in children?
What is DLGAP2?
Read the original research
Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.
Epigenetics, 15(1-2), 161-173
Citation
Schrott, Rose; Acharya, Kelly; Itchon-Ramos, Nilda; Hawkey, Andrew B; Pippen, Erica; Mitchell, John T; Kollins, Scott H; Levin, Edward D; Murphy, Susan K. (2020). Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm.. Epigenetics, 15(1-2), 161-173. https://doi.org/10.1080/15592294.2019.1656158
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