Gestational exposure to cannabidiol leads to glucose intolerance in 3-month-old male offspring.

Autor: Vanin SR; Departments of Obstetrics and Gynaecology, and Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada., Lee K; Departments of Obstetrics and Gynaecology, and Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada., Nashed M; Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada., Tse B; Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, The Lawson Health Research Institute and Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada., Sarikahya M; Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada., Brar S; Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, The Lawson Health Research Institute and Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada., Tomy G; Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada., Lucas AM; Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada., Tomy T; Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada., Laviolette SR; Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada., Arany EJ; Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, The Lawson Health Research Institute and Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada., Hardy DB; Departments of Obstetrics and Gynaecology, and Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.; The Lawson Health Research Institute and the Children's Health Research Institute, London, Ontario, Canada.
Jazyk: angličtina
Zdroj: The Journal of endocrinology [J Endocrinol] 2023 Nov 23; Vol. 260 (1). Date of Electronic Publication: 2023 Nov 23 (Print Publication: 2024).
DOI: 10.1530/JOE-23-0173
Abstrakt: Reports in North America suggest that up to 20% of young women (18-24 years) use cannabis during pregnancy. This is concerning given clinical studies indicate that maternal cannabis use is associated with fetal growth restriction and dysglycemia in the offspring. Preclinical studies demonstrated that prenatal exposure to Δ9-tetrahydrocannabinol, the main psychoactive component of cannabis, in rat dams led to female-specific deficits in β-cell mass and glucose intolerance/insulin resistance. Yet to date, the contributions of cannabidiol (CBD), the primary nonpsychoactive compound in cannabis, remain elusive. This study aimed to define the effects of in utero cannabidiol (CBD) exposure on postnatal glucose regulation. Pregnant Wistar rat dams received daily intraperitoneal injections of either a vehicle solution or 3 mg/kg of CBD from gestational day (GD) 6 to parturition. CBD exposure did not lead to observable changes in maternal or neonatal outcomes; however, by 3 months of age male CBD-exposed offspring exhibited glucose intolerance despite no changes in pancreatic β/α-cell mass. Transcriptomic analysis on the livers of these CBD-exposed males revealed altered gene expression of circadian rhythm clock machinery, which is linked to systemic glucose intolerance. Furthermore, alterations in hepatic developmental and metabolic processes were also observed, suggesting gestational CBD exposure has a long-lasting detrimental effect on liver health throughout life. Collectively, these results indicate that exposure to CBD alone in pregnancy may be detrimental to the metabolic health of the offspring later in life.
Databáze: MEDLINE