Physiology and Pharmacology Publications

Document Type

Article

Publication Date

2-2024

Journal

Cannabis and Cannabinoid Research

URL with Digital Object Identifier

10.1089/can.2023.0166

Abstract

Introduction: Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as ‘‘natural’’ and ‘‘safe’’ as it is non-intoxicating. In utero, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of D9-THC, there has been limited investigation into the impacts of in utero gestational CBD exposure on the placenta. Methods: This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat placentas from vehicle and CBD (3 mg/kg intraperitoneal injection) exposed pregnancies (E6.5-18.5). Results: The study revealed that pups from CBD-exposed pregnancies were 10% smaller, with the placentae displaying a decreased fetal blood space perimeter-to-area ratio. The transcriptomic analysis supported compromised angiogenesis and blood vessel formation with downregulated biological processes, including tube morphogenesis, angiogenesis, blood vessel morphogenesis, blood vessel development and vasculature development. Further, the CBD-exposed placentas displayed changed expression of glucose transporters (decreased GLUT1 and GR expression and increased GLUT3 expression). Transcriptomic analysis further revealed upregulated biological processes associated with metabolism. Finally, histological and transcriptomic analysis revealed altered cell populations within the placenta, specifically to syncytiotrophoblast layer II and endothelial cells. Conclusion: Together these results suggest that the structural changes in CDB-exposed placentae, including the altered expression of nutrient transporters and the changes to the placental fetal vasculature, may underlie the reduced fetal growth.

https://www.liebertpub.com/doi/10.1089/can.2023.0166

Notes

This is the accepted manuscript. final PDF available at

https://www.liebertpub.com/doi/10.1089/can.2023.0166

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Citation of this paper:

Allen S, Natale BV, Ejeckam AO, Lee K, Hardy DB, Natale DRC (2024) Cannabidiol exposure during rat pregnancy leads to labyrinth-specific vascular defects in the placenta and reduced fetal growth, Cannabis and Cannabinoid Research X:X, 1–15, DOI: 10.1089/ can.2023.0166.

https://www.liebertpub.com/doi/10.1089/can.2023.0166

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