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Open AccessReview

The Epigenetics of the Endocannabinoid System

Dipartimento di Scienze Motorie e del Benessere, Università di Napoli Parthenope, via Medina 40, 80133 Napoli, Italy
Dipartimento di Medicina, Chirurgia e Odontoiatria “Scuola Medica Salernitana”, Università degli Studi di Salerno, Via S Allende Baronissi, 84081 Salerno, Italy
Dipartimento di Medicina Sperimentale, Università della Campania L. Vanvitelli, via Costantinopoli 16, 80138 Cord Napoli, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(3), 1113;
Received: 8 January 2020 / Revised: 3 February 2020 / Accepted: 4 February 2020 / Published: 7 February 2020
The endocannabinoid system (ES) is a cell-signalling system widely distributed in biological tissues that includes endogenous ligands, receptors, and biosynthetic and hydrolysing machineries. The impairment of the ES has been associated to several pathological conditions like behavioural, neurological, or metabolic disorders and infertility, suggesting that the modulation of this system may be critical for the maintenance of health status and disease treatment. Lifestyle and environmental factors can exert long-term effects on gene expression without any change in the nucleotide sequence of DNA, affecting health maintenance and influencing both disease load and resistance. This potentially reversible “epigenetic” modulation of gene expression occurs through the chemical modification of DNA and histone protein tails or the specific production of regulatory non-coding RNA (ncRNA). Recent findings demonstrate the epigenetic modulation of the ES in biological tissues; in the same way, endocannabinoids, phytocannabinoids, and cannabinoid receptor agonists and antagonists induce widespread or gene-specific epigenetic changes with the possibility of trans-generational epigenetic inheritance in the offspring explained by the transmission of deregulated epigenetic marks in the gametes. Therefore, this review provides an update on the epigenetics of the ES, with particular attention on the emerging role in reproduction and fertility. View Full-Text
Keywords: endocannabinoids; endocannabinoid system; epigenetics; Δ9THC; DNA methylation; histone modifications; non coding RNA; reproduction; spermatozoa endocannabinoids; endocannabinoid system; epigenetics; Δ9THC; DNA methylation; histone modifications; non coding RNA; reproduction; spermatozoa
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Meccariello, R.; Santoro, A.; D'Angelo, S.; Morrone, R.; Fasano, S.; Viggiano, A.; Pierantoni, R. The Epigenetics of the Endocannabinoid System. Int. J. Mol. Sci. 2020, 21, 1113.

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