A specific gene associated with autism appears to undergo changes in the sperm of men who use marijuana, according to new research from Duke Health.
The gene change occurs through a process called DNA methylation, and it could potentially be passed along to offspring.
Publishing online Aug. 27 in the journal Epigenetics, the researchers said the findings do not establish a definitive link between cannabis use and autism, but the possible connection warrants further, urgent study, given efforts throughout the country 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,” said senior author Susan Murphy, Ph.D., associate professor in the Department of Obstetrics & Gynecology at Duke University School of Medicine.
Murphy and colleagues, including lead author and Ph.D. 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, the researchers noted several gene alterations in the sperm of men who smoke marijuana.
The current study homed in on specific genes, notably one called Discs-Large Associated Protein 2, or 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 said.
“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 unknown at this time.
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 said.
“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 said the study’s sample size was small – including 24 men, half who used marijuana and half who didn’t – and could not account for confounding factors such as diet, sleep and exercise, but 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 said.
“There’s a perception that marijuana is benign. More studies are needed to determine whether that is true.”
Provided by Duke University Medical Center
As recent research shows, men in Western countries are facing a fertility crisis. Sperm count in males of reproductive age more than halved between 1973 and 2011.
According to the Eunice Kennedy Shriver National Institute of Child Health and Human Development, approximately 9 percent of men in the United States have faced infertility.
For this reason, researchers have been looking at how different modifiable factors, such as lifestyle choices, might affect male fertility.
In a new study, a team of investigators from the Harvard T. H. Chan School of Public Health in Boston, MA, has focused on the effects that smoking marijuana has on markers of male fertility.
The researchers’ findings, which they report in a study paper that features in the journal Human Reproduction, ran counter to the hypothesis that they established at the beginning of the study.
“[The] unexpected findings highlight how little we know about the reproductive health effects of marijuana and, in fact, of the health effects of marijuana in general,” notes study author Jorge Chavarro.
“Our results need to be interpreted with caution, and they highlight the need to further study the health effects of marijuana use,” he emphasizes.
Higher sperm concentration among users
To begin with, the research team speculated that men who either smoked or had smoked marijuana would have poor sperm quality. However, that is not the conclusion that this study reached.
In their research, the investigators recruited 662 men who attended the Fertility Clinic at Massachusetts General Hospital in Boston between 2000 and 2017. The average participant was 36 years old, white, and had a college degree.
To assess sperm quality, the researchers collected and analyzed 1,143 semen samples from the study participants. They also took blood samples from 317 of the men. The team used the blood samples to test for reproductive hormones.
Additionally, the researchers asked the men to fill in questionnaires asking them about their use of marijuana, including whether they had ever smoked more than two joints and whether they still used marijuana.
The team found that 365 (or 55 percent) of the participants had smoked marijuana at some point in their lives. Of these people, 44 percent no longer used this substance, while 11 percent self-identified as current smokers.
In looking at the semen samples, the researchers noticed that men who had used marijuana had higher average sperm concentrations than nonsmokers.
More specifically, marijuana users had an average sperm concentration of 62.7 million sperm per milliliter of ejaculate, whereas their peers who had never smoked marijuana had 45.4 million sperm per milliliter of ejaculate.
The investigators also observed that among marijuana smokers, only 5 percent had sperm concentrations below 15 million sperm per milliliter of ejaculate — the threshold for “normal” sperm concentration levels — while 12 percent of never-smokers had sperm concentrations below this level.
Findings consistent with interpretations
Another finding reported in the study indicates that marijuana smokers who used the substance more frequently also tended to have higher blood testosterone levels.
Still, the researchers warn that their results may not apply to the general male population since the study focused specifically on men seeking treatment at a fertility clinic.
Even though they were unexpected, the authors suggest that their findings do make logical sense in the context of marijuana’s effect on the human endocannabinoid system, which responds to the active compounds present in this substance.
“Our findings were contrary to what we initially hypothesized. However, they are consistent with two different interpretations, the first being that low levels of marijuana use could benefit sperm production because of its effect on the endocannabinoid system, which is known to play a role in fertility, but those benefits are lost with higher levels of marijuana consumption.”
Lead author Feiby Nassan
“An equally plausible interpretation is that our findings could reflect the fact that men with higher testosterone levels are more likely to engage in risk-seeking behaviors, including smoking marijuana,” Nassan adds.
