Gene linked to autism undergoes changes in men's sperm after pot use
Further study is needed to determine if the altered gene contributes to autism in children
August 27, 2019
Science Daily/Duke University Medical Center
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."
https://www.sciencedaily.com/releases/2019/08/190827123515.htm
Exposure to cannabis alters the genetic profile of sperm
Marijuana growing. THC appeared to impact hundreds of different genes in rats and humans, but many of the genes did have something in common -- they were associated with two of the same major cellular pathways. Credit: © watman / Fotolia
Whether genetic changes can be reversed or are passed on to children is still unknown
December 19, 2018
Science Daily/Duke University Medical Center
New research suggests men in their child-bearing years should consider how THC could impact their sperm and possibly the children they conceive during periods when they've been using the drug. Much like previous research that has shown tobacco smoke, pesticides, flame retardants and even obesity can alter sperm, the new research shows THC also affects epigenetics, triggering structural and regulatory changes in the DNA of users' sperm.
As legal access to marijuana continues expanding across the U.S., more scientists are studying the effects of its active ingredient, tetrahydrocannabinol (THC), in teens, adults and pregnant women.
New research from Duke Health suggests men in their child-bearing years should also consider how THC could impact their sperm and possibly the children they conceive during periods when they've been using the drug.
Much like previous research that has shown tobacco smoke, pesticides, flame retardants and even obesity can alter sperm, the Duke research shows THC also affects epigenetics, triggering structural and regulatory changes in the DNA of users' sperm.
Experiments in rats and a study with 24 men found that THC appears to target genes in two major cellular pathways and alters DNA methylation, a process essential to normal development.
The researchers do not yet know whether DNA changes triggered by THC are passed to users' children and what effects that could have. Their findings will be published online Dec. 19 in the journal Epigenetics.
"What we have found is that the effects of cannabis use on males and their reproductive health are not completely null, in that there's something about cannabis use that affects the genetic profile in sperm," said Scott Kollins, Ph.D., professor in psychiatry and behavioral sciences at Duke and senior author of the study.
"We don't yet know what that means, but the fact that more and more young males of child-bearing age have legal access to cannabis is something we should be thinking about," Kollins said.
National research has shown a steady decline in the perceived risk of regular marijuana use. This, combined with the demand and wide availability of marijuana bred specifically to yield higher THC content, make this research especially timely, Kollins said.
The study defined regular users as those who smoked marijuana at least weekly for the previous six months. Their sperm were compared to those who had not used marijuana in the past six months and not more than 10 times in their lifetimes.
The higher the concentration of THC in the men's urine, the more pronounced the genetic changes to their sperm were, the authors found.
THC appeared to impact hundreds of different genes in rats and humans, but many of the genes did have something in common -- they were associated with two of the same major cellular pathways, said lead author Susan K. Murphy, Ph.D., associate professor and chief of the Division of Reproductive Sciences in obstetrics and gynecology at Duke.
One of the pathways is involved in helping bodily organs reach their full size; the other involves a large number of genes that regulate growth during development. Both pathways can become dysregulated in some cancers.
"In terms of what it means for the developing child, we just don't know," Murphy said. It's unknown whether sperm affected by THC could be healthy enough to even fertilize an egg and continue its development into an embryo, she said.
The study was a starting point on the epigenetic effects of THC on sperm and is limited by the relatively small number of men involved in the trial, Murphy said. The findings in men also could be confounded by other factors affecting their health, such as their nutrition, sleep, alcohol use and other lifestyle habits.
The Duke team plans to continue its research with larger groups. They intend to study whether changes in sperm are reversed when men stop using marijuana. They also hope to test the umbilical cord blood of babies born to fathers with THC-altered sperm to determine what, if any epigenetic changes, are carried forward to the child.
"We know that there are effects of cannabis use on the regulatory mechanisms in sperm DNA, but we don't know whether they can be transmitted to the next generation," Murphy said.
"In the absence of a larger, definitive study, the best advice would be to assume these changes are going to be there," Murphy said. "We don't know whether they are going to be permanent. I would say, as a precaution, stop using cannabis for at least six months before trying to conceive."
In addition to Kollins and Murphy, study authors include Nilda Itchon-Ramos, Zachary Visco, Zhiqing Huang, Carole Grenier, Rose Schrott, Kelly Acharya, Marie-Helene Boudreau, Thomas M. Price, Douglas J. Raburn, David L. Corcoran, Joseph E. Lucas, John T. Mitchell, F. Joseph McClernon, Marty Cauley, Brandon J. Hall, and Edward D. Levin.
The research was supported by a grant from the John Templeton Foundation.
https://www.sciencedaily.com/releases/2018/12/181219075846.htm