Epigenetic alterations in cytochrome P450 oxidoreductase (Por) in sperm of rats exposed to tetrahydrocannabinol (THC).

Abstract

As marijuana legalization is increasing, research regarding possible long-term risks for users and their offspring is needed. Little data exists on effects of paternal tetrahydrocannabinol (THC) exposure prior to reproduction. This study determined if chronic THC exposure alters sperm DNA methylation (DNAm) and if such effects are intergenerationally transmitted. Adult male rats underwent oral gavage with THC or vehicle control. Differentially methylated (DM) loci in motile sperm were identified using reduced representation bisulfite sequencing (RRBS). Another cohort was injected with vehicle or THC, and sperm DNAm was analyzed. Finally, THC-exposed and control adult male rats were mated with THC-naïve females. DNAm levels of target genes in brain tissues of the offspring were determined by pyrosequencing. RRBS identified 2,940 DM CpGs mapping to 627 genes. Significant hypermethylation was confirmed (p < 0.05) following oral THC administration for cytochrome P450 oxidoreductase (Por), involved in toxin processing and disorders of sexual development. Por hypermethylation was not observed after THC injection or in the subsequent generation. These results support that THC alters DNAm in sperm and that route of exposure can have differential effects. Although we did not observe evidence of intergenerational transmission of the DNAm change, larger studies are required to definitively exclude this possibility.

Department

Description

Provenance

Subjects

Citation

Published Version (Please cite this version)

10.1038/s41598-020-69204-7

Publication Info

Acharya, Kelly S, Rose Schrott, Carole Grenier, Zhiqing Huang, Zade Holloway, Andrew Hawkey, Edward D Levin, Susan K Murphy, et al. (2020). Epigenetic alterations in cytochrome P450 oxidoreductase (Por) in sperm of rats exposed to tetrahydrocannabinol (THC). Scientific reports, 10(1). p. 12251. 10.1038/s41598-020-69204-7 Retrieved from https://hdl.handle.net/10161/21204.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.