Cannabis use altered DNA methylation in human and rat sperm, with changes in cancer and developmental pathways | Research

The takeaway

A study found that cannabis use was associated with altered DNA methylation at nearly 4,000 sites in human sperm, with enrichment in Hippo Signaling and cancer pathways. The same pathways were affected in THC-exposed rat sperm, and cannabis use was also linked to lower sperm concentration.

Reproductive medicine researchers; epigenetics scientists; men considering fatherhood who use cannabis; clinicians counseling couples about preconception health.

3,979 methylation sites altered in cannabis users' sperm, with cross-species validation in rats

What the researchers found

Researchers compared DNA methylation in sperm from human cannabis users versus non-users, and from THC-exposed versus unexposed rats.

In human sperm, cannabis users differed from non-users by at least 10% methylation at 3,979 CpG sites.

Pathway analysis identified Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched in THC-exposed rat sperm (p < 0.01), providing cross-species validation.

THC exposure levels in humans correlated significantly with methylation changes for 177 genes, suggesting a dose-response relationship.

There was substantial overlap between genes with altered methylation in rat sperm (this study) and genes previously reported as having altered methylation in the brains of rat offspring born to THC-exposed parents.

Cannabis use in humans was also associated with significantly lower sperm concentration.

Why it matters

This is among the first studies to show that cannabis use alters the epigenetic signature of sperm in ways that affect developmental pathways, with potential implications for offspring. The cross-species replication strengthens the finding, and the overlap with offspring brain methylation patterns raises intergenerational concerns.

The numbers in context

3,979 CpG sites differed by ≥10% between cannabis users and non-users. Hippo Signaling and Cancer pathways enriched (Bonferroni p < 0.02 in humans, p < 0.01 in rats). 177 genes showed dose-response correlation with THC levels. Cannabis use associated with lower sperm concentration.

How the study worked

Cross-sectional human comparison (cannabis users vs non-users) and controlled rat experiment (THC vs vehicle). DNA methylation by reduced representation bisulfite sequencing. Pathway analysis. Correlation of THC levels with methylation. Sperm concentration measurement.

What this study cannot tell us

Human component is cross-sectional (cannabis users may differ in other ways). Small sample sizes in both human and rat studies. Methylation changes in sperm do not necessarily translate to functional changes in offspring. Reduced sperm concentration could have multiple causes.

How to read the evidence

Moderate. Novel findings with cross-species validation and dose-response data, but small samples and inability to prove functional consequences in offspring limit conclusions.

When this study was published

Published in 2018. Paternal cannabis exposure epigenetics has become an active research area since this publication.

The bigger picture

Epigenetic changes in sperm could theoretically be transmitted to offspring, affecting their development. While this study cannot prove that paternal cannabis use harms children, the overlap between sperm methylation changes and offspring brain methylation patterns in rats is a serious signal that warrants further investigation.

Questions still open

Do these sperm methylation changes reverse with cannabis cessation? Are offspring of cannabis-using fathers at measurable developmental risk? Which specific methylation changes are most functionally significant? Does the Hippo Signaling pathway disruption affect embryonic development?

Common questions

Could a father's cannabis use affect his future children?

This study found that cannabis alters DNA methylation in sperm, and some of these changes overlap with brain methylation patterns seen in rat offspring of THC-exposed parents. This raises the possibility of paternal transmission, but direct evidence of harm to human offspring has not been established.

What is the Hippo Signaling pathway?

Hippo Signaling is a pathway that controls organ size, cell growth, and tissue development. It plays critical roles during embryonic development. Disruption of this pathway in sperm DNA methylation could theoretically affect how genes are expressed during early development of offspring.

Read the original research

Cannabinoid exposure and altered DNA methylation in rat and human sperm.

Epigenetics, 13(12), 1208-1221

View on PubMed ↗Publisher’s paper ↗

Citation

Murphy, Susan K; Itchon-Ramos, Nilda; Visco, Zachary; Huang, Zhiqing; Grenier, Carole; Schrott, Rose; Acharya, Kelly; Boudreau, Marie-Helene; Price, Thomas M; Raburn, Douglas J; Corcoran, David L; Lucas, Joseph E; Mitchell, John T; McClernon, F Joseph; Cauley, Marty; Hall, Brandon J; Levin, Edward D; Kollins, Scott H. (2018). Cannabinoid exposure and altered DNA methylation in rat and human sperm.. Epigenetics, 13(12), 1208-1221. https://doi.org/10.1080/15592294.2018.1554521