Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin.
Animals
Autistic Disorder
/ genetics
Chromatin
/ chemistry
CpG Islands
/ drug effects
DNA Methylation
/ drug effects
Disease Models, Animal
Dronabinol
/ adverse effects
Epigenesis, Genetic
/ drug effects
Gene Regulatory Networks
/ drug effects
High-Throughput Nucleotide Sequencing
Male
Nicotine
/ adverse effects
Rats
Sequence Analysis, DNA
Spermatozoa
/ chemistry
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 09 2020
29 09 2020
Historique:
received:
11
03
2020
accepted:
03
09
2020
entrez:
30
9
2020
pubmed:
1
10
2020
medline:
14
1
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32994467
doi: 10.1038/s41598-020-72783-0
pii: 10.1038/s41598-020-72783-0
pmc: PMC7525661
doi:
Substances chimiques
Chromatin
0
Nicotine
6M3C89ZY6R
Dronabinol
7J8897W37S
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16022Subventions
Organisme : NIEHS NIH HHS
ID : T32 ES021432
Pays : United States
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