November 18, 2019

New study on sperm epigenetics published

Rose Schrott, a PhD candidate at Duke University won the 2019 Campion Fund Poster Presentation Award given at the Triangle Consortium for Reproductive Biology held at NIEHS in North Carolina.  Her outstanding poster presented work on the epigenetic alterations of sperm DNA due to exposure to cannabis, also called marijuana and we are proud to note its publication in the journal. Epigenetics. 

Previous studies show that mothers who use marijuana during pregnancy may have infants with decreased birth weights, possible impaired immune systems and increased admissions to a neonatal care unit.  Now, Rose and her colleagues have published the studies presented on her award poster showing that cannabis use in reproductive age men is associated with changes in the expression of an autism candidate gene in human sperm.  The published paper also reported findings of the gene in rats.  The human gene is DLGAP2 (Discs-Large Associated Protein 2) while the rat gene is Dlgap2.  This gene is involved in nerve synapse organization, neuronal signaling and is strongly implicated in autism and schizophrenia.  DLGAP2 is paternally expressed in the testis and biallelically expressed in the brain, but has very low expression in other tissues of the body.  Dr. Schrott and colleagues demonstrated that in humans, 17 gene CpG sites were hypomethylated, nine in Intron 7 of the gene.   These sites were 72.5 differentially methylated indicating that they are not imprinted sites.  Dr. Schrott and colleagues conducted careful epigenetic studies of 12 men aged 18-40 years who were cannabis users defined by history and urine testing and 12 men of the same age who were non-users.  The research found that cannabis exposure will cause hypomethylation of the DLGAP2 gene in sperm.  Compared to control young men, those exposed to cannabis had DLGAP2 DNA with a significant loss of intron 7.  The researchers also demonstrated an increased DLGAP2 expression in the brains of 28 conceptuses.  The study also reported similar findings of the Dlgap2 DNA in adult male rats treated with tetrahydrocannabinol (THC) and in the brains of their offspring.  There was increased expression of Dlgap2 in the nucleus accumbens, a part of the brain responsible for the cognitive processing of reward, motivation, and aversion.  This important study suggests that that cannabis exposure in men of reproductive age contributes to the disruption of sperm DNA methylation and that these changes could be transmitted to subsequent generations.

Dr. Schrott’s study indicates that the use of cannabis in reproductive age males is not risk-free.  Given that the percentage of adults who believe that cannabis use is risky has declined in the US and that 15% of adults think that there are no health risks in cannabis use the implications for health care policy is tremendous. Strong educational programs to educate men contemplating having children of the risks in cannabisuse are now essential for reproductive health.

Rose Schrott, Kelly Acharya, Nilda Itchon-Ramos, Andrew B. Hawkey, Erica Pippen, John T. Mitchell, Scott H. Kollins, Edward D. Levin & Susan Murphy (2019) Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm, Epigenetics, DOI: 10.1080/15592294.2019.1656158