Gene Linked to Autism Undergoes Changes in Men’s Sperm After Marijuana Use

Further study to determine whether altered gene contributes to childhood autism

image of sperm

A specific gene associated with autism appears to undergo changes in the sperm of men who use marijuana, according to new Duke research. The gene change occurs through a process called DNA methylation, and it could potentially be passed along to offspring.

In the study, published in August 2019 in Epigenetics, researchers reported the findings do not establish a definitive link between cannabis use and autism, but the possible connection warrants further study, given national efforts to legalize marijuana for recreational and/or medicinal uses.

“This study is the first to demonstrate an association between a man’s cannabis use and changes of a gene in sperm that has been implicated in autism,” says senior author Susan K. Murphy, PhD, associate professor in the Department of Obstetrics & Gynecology at Duke University School of Medicine.

Murphy and colleagues, including lead author and Duke PhD student Rose Schrott, conducted studies using human biologics and animal models to analyze differences between the sperm of males who smoked or ingested marijuana compared to a control group with no such exposures.

In earlier work, published in December 2018 in Epigenetics, the researchers noted several gene alterations in the sperm of men who use marijuana. The current study homed in on specific genes, notably Discs-Large Associated Protein 2 (DLGAP2). This gene is involved in transmitting neuron signals in the brain and has been strongly implicated in autism, as well as schizophrenia and post-traumatic stress disorder.

“We identified significant hypomethylation at DLGAP2 in the sperm of men who used marijuana compared to controls, as well as in the sperm of rats exposed to THC compared to controls,” Schrott says. “This hypomethylated state was also detected in the forebrain region of rats born to fathers exposed to THC, supporting the potential for intergenerational inheritance of an altered sperm DNA methylation pattern.”

The Duke team found that there was a sex-based difference in the relationship between DNA methylation and gene expression in human brain tissues. In both male and female brain tissues, increased DNA methylation was associated with decreased gene activity. This relationship was strongest in females, and seemed to be less well maintained in males, though the reason for this is currently unknown. This anomaly was notable, because the ratio of boys to girls with autism is 4:1, and there are sex differences in the neurobehavioral symptoms.

“It’s possible that the relationship between methylation and expression is modified if the methylation change we see in sperm is inherited by the offspring,” Murphy says. “In any event, it’s clear that the region of DNA methylation within DLGAP2 that is altered in association with cannabis use is functionally important in the brain.”

Murphy says the study’s sample size was small, with 24 participants. Twelve participants used marijuana and twelve did not. The study did not account for confounding factors such as diet, sleep, and exercise; however, the findings should prompt continued research.

“Given marijuana’s increasing prevalence of use in the U.S. and the increasing numbers of states that have legalized its use, we need more studies to understand how this drug is affecting not only those who smoke it, but their unborn children,” Murphy says. “There’s a perception that marijuana is benign. More studies are needed to determine whether that is true.”