Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin
Open Access
- 29 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-12
- https://doi.org/10.1038/s41598-020-72783-0
Abstract
Men consume the most nicotine and cannabis products but impacts on sperm epigenetics are poorly characterized. Evidence suggests that preconception exposure to these drugs alters offspring neurodevelopment. Epigenetics may in part facilitate heritability. We therefore compared effects of exposure to tetrahydrocannabinol (THC) and nicotine on DNA methylation in rat sperm at genes involved in neurodevelopment. Reduced representation bisulfite sequencing data from sperm of rats exposed to THC via oral gavage showed that seven neurodevelopmentally active genes were significantly differentially methylated versus controls. Pyrosequencing data revealed majority overlap in differential methylation in sperm from rats exposed to THC via injection as well as those exposed to nicotine. Neurodevelopmental genes including autism candidates are vulnerable to environmental exposures and common features may mediate this vulnerability. We discovered that autism candidate genes are significantly enriched for bivalent chromatin structure, suggesting this configuration may increase vulnerability of genes in sperm to disrupted methylation.Funding Information
- John Templeton Foundation (60564, 60957)
This publication has 61 references indexed in Scilit:
- Paternal obesity is associated with IGF2hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohortBMC Medicine, 2013
- SHANK1 Deletions in Males with Autism Spectrum DisorderAmerican Journal of Human Genetics, 2012
- Gender-specific methylation differences in relation to prenatal exposure to cigarette smokeGene, 2012
- Prenatal environmental exposures, epigenetics, and diseaseReproductive Toxicology, 2011
- Genes for embryo development are packaged in blocks of multivalent chromatin in zebrafish spermGenome Research, 2011
- Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domainsGenome Research, 2010
- Genomic and epigenetic evidence for oxytocin receptor deficiency in autismBMC Medicine, 2009
- Distinctive chromatin in human sperm packages genes for embryo developmentNature, 2009
- A stem cell–like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencingNature Genetics, 2007
- A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem CellsCell, 2006