ArticleToxicological sciences : an official journal of the Society of Toxicology2023
Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Prospective associations of premature senescence, inflammation, and MERCSs in the cardioprotective effect of CBD in HFpEF.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Network pharmacology identifies repurposable drugs targeting host pathways across the oral-gut-lung axis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mechanistic study of the cytotoxicity of cannabidiol and its metabolites in HepG2 cells.Archives of toxicology · 2026Article
- 7-Hydroxycannabidiol and 7-carboxycannabidiol induced cytotoxicity via apoptosis and endoplasmic reticulum stress in human hepatic cells.Archives of toxicology · 2025Article
- The impact of cannabinoids on reproductive function.Reproduction (Cambridge, England) · 2025Review
- Cannabis smoking is associated with persistent epigenome-wide disruptions despite smoking cessation.BMC pulmonary medicine · 2025Observational
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- Comparing the cannabidiol-induced transcriptomic profiles in human and mouse Sertoli cells.Toxicology · 2025Article
- Current marijuana use is associated with lower circulating α-Klotho levels in US adults even after adjusting for tobacco use: A national cross-sectional analysis of NHANES.Tobacco induced diseases · 2025Article
- Cannabinoids and healthy ageing: the potential for extending healthspan and lifespan in preclinical models with an emphasis on Caenorhabditis elegans.GeroScience · 2024Review
- Cannabidiol (CBD) modulates the transcriptional profile of ethanol-exposed human dermal fibroblast cells.Journal of applied genetics · 2024Article
- Toxicity of cannabidiol and its metabolites in TM3 mouse Leydig cells: a comparison with primary human Leydig cells.Archives of toxicology · 2024Article
- Persisting neurobehavioral consequences of daily or intermittent paternal cannabis administration in F1 and F2 Rats.Neurotoxicology · 2024Article
- Alzheimer's disease, aging, and cannabidiol treatment: a promising path to promote brain health and delay aging.Molecular biology reports · 2024Review
- Induction of apoptosis by cannabidiol and its main metabolites in human Leydig cells.Archives of toxicology · 2023Article
- In vitro evaluation of cell viability and expression profile of growth factors in mouse Sertoli cells exposed to Delta-9-tetrahydrocannabinol: a mechanistic insight into the cannabinoid-induced testicular toxicity.BMC pharmacology & toxicology · 2023Article
- The Polypharmacological Effects of Cannabidiol.Molecules (Basel, Switzerland) · 2023Review
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Authors and funding
7 authors at 3 institutions in 1 country.
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Abstract
Cannabidiol (CBD), one of the major cannabinoids in the plant Cannabis sativa L., is the active ingredient in a drug approved for the treatment of seizures associated with certain childhood-onset epileptic disorders. CBD has been shown to induce male reproductive toxicity in multiple animal models. We previously reported that CBD inhibits cellular proliferation in the mouse Sertoli cell line TM4 and in primary human Sertoli cells. In this study, using a transcriptomic approach with mRNA-sequencing analysis, we identified molecular mechanisms underlying CBD-induced cytotoxicity in primary human Sertoli cells. Analysis of differentially expressed genes demonstrated that DNA replication, cell cycle, and DNA repair were the most significantly affected pathways. We confirmed the concentration-dependent changes in the expression of key genes in these pathways using real-time PCR. mRNA sequencing showed upregulation of a group of genes tightly associated with the senescence-associated secretory phenotype (SASP) and with the activation of the p53 signaling pathway, a key upstream event in cellular senescence. Prolonged treatment of 10 μM CBD-induced cellular senescence, as evidenced by the stable cessation of proliferation and the activation of senescence-associated β-galactosidase (SA-β-gal), 2 hallmarks of senescence. Additionally, using real-time PCR and Western blotting assays, we observed that CBD treatment increased the expression of p16, an important marker of cellular senescence. Taken together, our results show that CBD exposure disturbs various interrelated signaling pathways and induces cellular senescence in primary human Sertoli cells.
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