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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 the early embryonic developmental cascade to investigate the impact of exposure to the most abundant phytocannabinoid, \u03949-tetrahydrocannabinol (\u03949-THC). We demonstrate that \u03949-THC increases the proliferation of naive 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, \u03949-THC capitalizes on ESCs\u2019 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 \u03949-THC exposure on early stages of germline development.<\/jats:p>","DOI":"10.7554\/elife.88795","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T12:13:15Z","timestamp":1689250395000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.88795","source":"Crossref","is-referenced-by-count":4,"title":["Metabolic memory of \u03949-tetrahydrocannabinol exposure in pluripotent stem cells and primordial germ cells-like cells"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-6720","authenticated-orcid":true,"given":"Roxane","family":"Verdikt","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046rm7j60","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Society and Genetics, University of California, Los Angeles","place":["Los Angeles, United 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