While most of the focus on developmental epigenomics puts mom in the spotlight, a recent surge in sperm studies are showing that dad’s dreams of a care-free lifestyle are up in smoke. We’ve already seen that a high-fat diet can alter the sperm epigenome, and now a factor that may encourage such half-baked decisions takes the spotlight. With the legalization of cannabis counties in countries and states, comes an important public health issue related not only to users but also their offspring, where a team from Duke University (North Carolina) now shows that cannabis can alter the DNA methylation profile of exposed sperm.
The talented team examined the effects of cannabis on human sperm and the effects of tetrahydrocannabinol (THC), an active ingredient of cannabis, on rat sperm through reduced representation bisulfite sequencing (RRBS) to assay DNA methylation.
Here’s what they found when the smoke cleared:
- In human cannabis smokers, sperm concentration is significantly lowered and 3,979 CpG sites show at least a 10% difference, with a preference for hypomethylation
- From a further filtered list, 183 CpGs sites belonging to 177 genes exhibit methylation levels that correlate with THC levels
- When comparing human and rat sperm RRBS:
- 99 genes exhibit a conserved response
- Gene functional analysis uncovered significant alterations in developmental pathways (hippo signaling pathway and pathways in cancer)
The team then compared their findings to a previous study examining offspring from rat parents exposed to THC during adolescence. This previous study revealed that offspring suffer from altered brain DNA methylation profiles and increased self-administration of heroin. By comparing the 627 genes from their newly acquired sperm methylomes to the 473 genes from the previous brain methylome study, the authors uncovered a significant overlap driven by 55 genes.
Senior author Scott Kollins shares, “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’tyet 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.”
First author Susan Murphy adds, “In terms of what it means for the developing child, we just don’t know. It’s unknown whether sperm affected by THC could be healthy enough to even fertilize an egg and continue its development into an embryo. We know that there are effects of cannabis use on the regulatory mechanisms in sperm DNA, but we don’tknow whether they can be transmittedto 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. 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.”
Go see why prospective fathers should pass on the puff, puff over in Epigenetics, December 2018