Cannabis-related sperm DNA changes were detectable in rat offspring, who also had enlarged hearts | Research

The takeaway

Rats exposed to cannabis extract had sperm DNA methylation changes that were detectable in their offspring's sperm and brain tissue, and their offspring had significantly enlarged hearts.

Researchers studying intergenerational effects of substance use, and prospective fathers interested in potential health impacts on offspring.

Offspring of cannabis-exposed fathers had significant cardiomegaly

What the researchers found

Cannabis extract exposure caused 3,321 differentially methylated sites in rat sperm, some of which persisted after a washout period. Select changes were detectable in offspring sperm and brain tissue, with a sex-specific relationship between methylation and gene expression. Offspring of exposed fathers had significant cardiomegaly.

Why it matters

This is the first study to characterize the entire rat sperm methylome after cannabis exposure and demonstrate that some changes are heritable, appearing in offspring tissues and associated with measurable health outcomes.

The numbers in context

3,321 differentially methylated CpGs identified in exposed sperm. Pxylp1 methylation changes in fathers were also detectable in offspring sperm. Mtss1l changes found in offspring hippocampus and nucleus accumbens. Offspring of exposed fathers had significant cardiomegaly.

How the study worked

Whole genome bisulfite sequencing of rat sperm across three groups: cannabis extract for 28 days then 56 days vehicle, vehicle then 28 days cannabis, or vehicle only. Males mated with drug-naive females. Offspring heart, brain, and sperm analyzed. Validated with bisulfite pyrosequencing.

What this study cannot tell us

This is a rat study, so direct translation to humans is uncertain. The cannabis extract dosing may not mirror typical human use. The mechanism linking sperm methylation changes to offspring cardiomegaly is not yet clear.

How to read the evidence

Preliminary: animal study, first of its kind, requires human replication.

When this study was published

Published in 2022.

The bigger picture

This study provides the strongest evidence to date that paternal cannabis exposure can create heritable epigenetic changes with functional consequences in offspring, challenging the assumption that fathers' pre-conception habits don't affect children.

Questions still open

Do human fathers who use cannabis produce offspring with similar heart enlargement? Is the cardiomegaly clinically significant or a benign finding? Could stopping cannabis use before conception reverse these sperm changes?

Common questions

Did the sperm changes persist after stopping cannabis?

Some methylation changes persisted even after a 56-day washout period (roughly one full spermatogenic cycle in rats), suggesting lasting effects.

How were the changes detected in offspring?

Methylation changes validated in fathers' sperm at specific genes (Pxylp1 and Mtss1l) were also found in offspring sperm and brain tissue, but not in control offspring.

What is cardiomegaly?

Cardiomegaly means an enlarged heart. In this study, rats born to cannabis-exposed fathers had significantly larger hearts than those born to control fathers, though the long-term health implications are not yet known.

Read the original research

Sperm DNA methylation alterations from cannabis extract exposure are evident in offspring.

Epigenetics & chromatin, 15(1), 33

View on PubMed ↗Publisher’s paper ↗

Citation

Schrott, Rose; Modliszewski, Jennifer L; Hawkey, Andrew B; Grenier, Carole; Holloway, Zade; Evans, Janequia; Pippen, Erica; Corcoran, David L; Levin, Edward D; Murphy, Susan K. (2022). Sperm DNA methylation alterations from cannabis extract exposure are evident in offspring.. Epigenetics & chromatin, 15(1), 33. https://doi.org/10.1186/s13072-022-00466-3