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Developmental Biology - Sperm Genetics

Cannabis Alters Genes in Sperm

Whether gene changes can be reversed or are passed on to children is still unknown...


New research from Duke Health suggests men in their child producing years consider not use cannibis because of THC (tetrahydrocannabinol). Much like previous research that has revealed tobacco smoke, pesticides, flame retardants and even obesity all can alter sperm, Duke research shows THC affects sperm, triggering structural and regulatory DNA alterations.

Experiments in rats along with this recent study of 24 men, finds THC targets genes in two major cell pathways altering DNA methylation, a process essential for normal sperm development. Researchers don't yet know whether DNA changes triggered by THC are passed onto the men's children, or what effects might result. Their findings are published 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. 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."

Scott Kollins PhD, Professor, Psychiatry and Behavioral Sciences, Duke University, and senior author of the study.

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 adds.
The study defined regular users as those who smoked marijuana weekly for the previous six months, comparing them to men who had not used marijuana in the past six months and not more than 10 times in their lifetimes. The authors found that higher concentration of THC in men's urine, displayed as more genetic changes in their sperm.

Susan K. Murphy PhD, is lead author on the study and Associate Professor and Chief of the Division of Reproductive Sciences, Obstetrics and gynecology at Duke, she explains: "In terms of what it means for the developing child, we just don't know." It's unknown whether sperm affected by THC are healthy enough to even fertilize an egg to continue developing into an embryo. THC appears to impact hundreds of different genes in rats and humans. Many are associated with two major cellular communication pathways: one impacting a large number of genes regulating all growth in utero, and another involved in each organ reaching its full size.

Murphy points out the study was conducted on a relatively small number of men and findings could be confounded by an individual's nutrition, sleep, alcohol use or other lifestyle habits. So, the Duke team plans to continue their research on larger male populations to see if changes in sperm genes are reversed when marijuana use is stopped. They also want to test umbilical cord blood of babies born to fathers with THC-altered sperm to determine what, if any, of these epigenetic changes are carried by 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. In the absence of a larger, definitive study, the best advice would be to assume these changes are going to be there. What we don't know is 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."

Susan K. Murphy PhD, Associate Professor and Chief, Division of Reproductive Sciences, Obstetrics and Gynecology, Duke University and lead author.

Abstract
Little is known about the reproductive effects of paternal cannabis exposure. We evaluated associations between cannabis or tetrahydrocannabinol (THC) exposure and altered DNA methylation in sperm from humans and rats, respectively. DNA methylation, measured by reduced representation bisulfite sequencing, differed in the sperm of human users from non-users by at least 10% at 3,979 CpG sites. Pathway analyses indicated Hippo Signaling and Pathways in Cancer as enriched with altered genes (Bonferroni p < 0.02). These same two pathways were also enriched with genes having altered methylation in sperm from THC-exposed versus vehicle-exposed rats (p < 0.01). Data validity is supported by significant correlations between THC exposure levels in humans and methylation for 177 genes, and substantial overlap in THC target genes in rat sperm (this study) and genes previously reported as having altered methylation in the brain of rat offspring born to parents both exposed to THC during adolescence. In humans, cannabis use was also associated with significantly lower sperm concentration. Findings point to possible pre-conception paternal reproductive risks associated with cannabis use.

Authors
Susan K. Murphy ORCID Icon, 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, Edward D. Levin and Scott H. Kollins.

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.

No potential conflict of interest was reported by the authors.


Acknowledgements
This research was supported a grant from the John Templeton Foundation. The opinions expressed in this publication are those of the authors and do not necessarily reflect the views of the John Templeton Foundation. We thank Drs. Andrew Berchuck and Matthew Barber for critical review of the manuscript. We thank the study participants and gratefully acknowledge the expert assistance of Sabrina Simpson and Jamie Wylie..

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Dec 20, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




As legal access to marijuana continues expanding across the USA, more scientists are studying the effects of its active ingredient, tetrahydrocannabinol (THC), in teens, adults and pregnant women.


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