Metabolic memory of Δ9-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells.
Roxane Verdikt, Abigail A Armstrong, Jenny Cheng, Young Sun Hwang, Amander T Clark, Xia Yang, Patrick Allard
bioRxiv October 2, 2023 preprint DOI: 10.1101/2023.03.13.531968 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study |
|---|---|
| Population | Naïve and primed mouse embryonic stem cells and their differentiated Primordial Germ Cell-Like Cells |
| Intervention | Δ9-tetrahydrocannabinol (Δ9-THC) |
| Topics | Cannabis |
| Keywords | Metabolism Embryonic stem cells Primordial germ cells δ9-THC |
| Key findings | Δ9-THC increased proliferation of naïve mouse embryonic stem cells, but not primed cells, in a CB1 receptor-dependent manner, with only moderate transcriptomic changes. The compound increased glycolytic rates and anabolic capabilities, and this metabolic rewiring persisted through differentiation into Primordial Germ Cell-Like Cells without direct exposure, accompanied by altered transcriptional profiles. |
Abstract
Cannabis, the most consumed illicit psychoactive drug in the world, is increasingly used by pregnant women. However, while cannabinoid receptors are expressed in the early embryo, the impact of phytocannabinoids exposure on early embryonic processes is lacking. Here, we leverage a stepwise in vitro differentiation system that captures early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, Δ9-tetrahydrocannabinol (Δ9-THC). We demonstrate that Δ9-THC increases the proliferation of naïve mouse embryonic stem cells (ESCs) but not of their primed counterpart. Surprisingly, this increased proliferation, dependent on the CB1 receptor binding, is only associated with moderate transcriptomic changes. Instead, Δ9-THC capitalizes on ESCs' metabolic bivalence by increasing their glycolytic rates and anabolic capabilities. A memory of this metabolic rewiring is retained throughout differentiation to Primordial Germ Cell-Like Cells in the absence of direct exposure and is associated with an alteration of their transcriptional profile. These results represent the first in-depth molecular characterization of the impact of Δ9-THC exposure on early stages of germline development.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 4
- Adolescent exposure to Δ9-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons. Molecular Psychiatry April 2019
- Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex. Journal of Psychiatry and Neuroscience March 2018
- High times for cannabis: Epigenetic imprint and its legacy on brain and behavior. Neuroscience & Biobehavioral Reviews February 2018
- Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure. Neuropsychopharmacology December 2015