{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:16:12Z","timestamp":1790018172647,"version":"4.0.1"},"reference-count":102,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"NSERC Discovery","doi-asserted-by":"publisher","award":["RGPIN-2020-06739"],"award-info":[{"award-number":["RGPIN-2020-06739"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Michael DeGroote Medicinal Cannabis Research Centre","award":["RGPIN-2020-06739"],"award-info":[{"award-number":["RGPIN-2020-06739"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Trophoblast differentiation is a crucial process in the formation of the placenta where cytotrophoblasts (CTs) differentiate and fuse to form the syncytiotrophoblast (ST). The bioactive components of cannabis, such as \u03949-THC, are known to disrupt trophoblast differentiation and fusion, as well as mitochondrial dynamics and respiration. However, less is known about the impact of cannabidiol (CBD) on trophoblast differentiation. Due to the central role of mitochondria in stem cell differentiation, we evaluated the impact of CBD on trophoblast mitochondrial function and differentiation. Using BeWo b30 cells, we observed decreased levels of mRNA for markers of syncytialization (GCM1, ERVW1, hCG) following 20 \u00b5M CBD treatment during differentiation. In CTs, CBD elevated transcript levels for the mitochondrial and cellular stress markers HSP60 and HSP70, respectively. Furthermore, CBD treatment also increased the lipid peroxidation and oxidative damage marker 4-hydroxynonenal. Mitochondrial membrane potential, basal respiration and ATP production were diminished with the 20 \u00b5M CBD treatment in both sub-lineages. mRNA levels for endocannabinoid system (ECS) components (FAAH, NAPEPLD, TRPV1, CB1, CB2, PPAR\u03b3) were altered differentially by CBD in CTs and STs. Overall, we demonstrate that CBD impairs trophoblast differentiation and fusion, as well as mitochondrial bioenergetics and redox homeostasis.<\/jats:p>","DOI":"10.3390\/cells13060486","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T07:25:32Z","timestamp":1710141932000},"page":"486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cannabidiol Disrupts Mitochondrial Respiration and Metabolism and Dysregulates Trophoblast Cell Differentiation"],"prefix":"10.3390","volume":"13","author":[{"given":"Tina","family":"Podinic","sequence":"first","affiliation":[{"name":"Graduate Program in Medical Sciences, Department of Pediatrics, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Limoges","sequence":"additional","affiliation":[{"name":"Graduate Program in Medical Sciences, Department of Pediatrics, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Monaco","sequence":"additional","affiliation":[{"name":"Graduate Program in Medical Sciences, Department of Pediatrics, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andie","family":"MacAndrew","sequence":"additional","affiliation":[{"name":"Graduate Program in Medical Sciences, Department of Pediatrics, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahek","family":"Minhas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"},{"name":"Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Nederveen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"},{"name":"Department of Kinesiology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Raha","sequence":"additional","affiliation":[{"name":"Graduate Program in Medical Sciences, Department of Pediatrics, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.17269\/s41997-018-0148-0","article-title":"Trends and correlates of cannabis use in pregnancy: A population-based study in Ontario, Canada from 2012 to 2017","volume":"110","author":"Corsi","year":"2019","journal-title":"Can. 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