Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin

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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.

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Modeling autism by SHANK gene mutations in mice.

Yong-Hui Jiang, Michael Ehlers (2013)

Shank family proteins (Shank1, Shank2, and Shank3) are synaptic scaffolding proteins that organize an extensive protein complex at the postsynaptic density (PSD) of excitatory glutamatergic synapses. Recent human genetic studies indicate that SHANK family genes (SHANK1, SHANK2, and SHANK3) are causative genes for idiopathic autism spectrum disorders (ASD). Neurobiological studies of Shank mutations in mice support a general hypothesis of synaptic dysfunction in the pathophysiology of ASD. However, the molecular diversity of SHANK family gene products, as well as the heterogeneity in human and mouse phenotypes, pose challenges to modeling human SHANK mutations. Here, we review the molecular genetics of SHANK mutations in human ASD and discuss recent findings where such mutations have been modeled in mice. Conserved features of synaptic dysfunction and corresponding behaviors in Shank mouse mutants may help dissect the pathophysiology of ASD, but also highlight divergent phenotypes that arise from different mutations in the same gene. Copyright © 2013 Elsevier Inc. All rights reserved.

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Prenatal environmental exposures, epigenetics, and disease.

Frederica Perera, Julie Herbstman (2011)

This review summarizes recent evidence that prenatal exposure to diverse environmental chemicals dysregulates the fetal epigenome, with potential consequences for subsequent developmental disorders and disease manifesting in childhood, over the lifecourse, or even transgenerationally. The primordial germ cells, embryo, and fetus are highly susceptible to epigenetic dysregulation by environmental chemicals, which can thereby exert multiple adverse effects. The data reviewed here on environmental contaminants have potential implications for risk assessment although more data are needed on individual susceptibility to epigenetic alterations and their persistence before this information can be used in formal risk assessments. The findings discussed indicate that identification of environmental chemicals that dysregulate the prenatal epigenome should be a priority in health research and disease prevention. Copyright © 2011 Elsevier Inc. All rights reserved.

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US Epidemiology of Cannabis Use and Associated Problems

Deborah Hasin (2017)

This review provides an overview of the changing US epidemiology of cannabis use and associated problems. Adults and adolescents increasingly view cannabis as harmless, and some can use cannabis without harm. However, potential problems include harms from prenatal exposure and unintentional childhood exposure; decline in educational or occupational functioning after early adolescent use, and in adulthood, impaired driving and vehicle crashes; cannabis use disorders (CUD), cannabis withdrawal, and psychiatric comorbidity. Evidence suggests national increases in cannabis potency, prenatal and unintentional childhood exposure; and in adults, increased use, CUD, cannabis-related emergency room visits, and fatal vehicle crashes. Twenty-nine states have medical marijuana laws (MMLs) and of these, 8 have recreational marijuana laws (RMLs). Many studies indicate that MMLs or their specific provisions did not increase adolescent cannabis use. However, the more limited literature suggests that MMLs have led to increased cannabis potency, unintentional childhood exposures, adult cannabis use, and adult CUD. Ecological-level studies suggest that MMLs have led to substitution of cannabis for opioids, and also possibly for psychiatric medications. Much remains to be determined about cannabis trends and the role of MMLs and RMLs in these trends. The public, health professionals, and policy makers would benefit from education about the risks of cannabis use, the increases in such risks, and the role of marijuana laws in these increases.

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Author and article information

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Susan K. Murphy: susan.murphy@duke.edu

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 29 September 2020

Publication date PMC-release: 29 September 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 16022

Affiliations

[1 ]GRID grid.189509.c, ISNI 0000000100241216, Division of Reproductive Sciences, Department of Obstetrics and Gynecology, , Duke University Medical Center, ; Chesterfield Building, 701 W. Main Street, Suite 510, Durham, NC 27701 USA

[2 ]GRID grid.26009.3d, ISNI 0000 0004 1936 7961, Integrated Toxicology and Environmental Health Program, Nicholas School of the Environment, , Duke University, ; Durham, NC USA

[3 ]GRID grid.189509.c, ISNI 0000000100241216, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, , Duke University Medical Center, ; Durham, NC USA

[4 ]GRID grid.189509.c, ISNI 0000000100241216, Division of Surgical Sciences, Department of Surgery, Center for Applied Therapeutics, , Duke University Medical Center, ; Durham, NC USA

[5 ]GRID grid.189509.c, ISNI 0000000100241216, Department of Psychiatry and Behavioral Sciences, , Duke University Medical Center, ; Durham, NC USA

[6 ]GRID grid.189509.c, ISNI 0000000100241216, Department of Pathology, , Duke University Medical Center, ; Durham, NC USA

Article

Publisher ID: 72783

DOI: 10.1038/s41598-020-72783-0

PMC ID: 7525661

PubMed ID: 32994467

SO-VID: 4427d7d2-75e5-4e78-9d3e-ad2944ed939e

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 11 March 2020

Date accepted : 3 September 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000925, John Templeton Foundation;

Award ID: 60564

Award ID: 60957

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ScienceOpen disciplines: Uncategorized

Keywords: dna methylation,epigenomics,spermatogenesis,autism spectrum disorders

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ScienceOpen disciplines: Uncategorized

Keywords: dna methylation, epigenomics, spermatogenesis, autism spectrum disorders

Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin

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Journal for ReAttach Therapy and Developmental Diversities

Most cited references 45

Modeling autism by SHANK gene mutations in mice.

Prenatal environmental exposures, epigenetics, and disease.

US Epidemiology of Cannabis Use and Associated Problems

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