Maternal exposure to Δ9-tetrahydrocannabinol impairs female offspring glucose homeostasis and endocrine pancreatic development in the rat.

Autor: Gillies R; Department of Pathology and Laboratory Medicine, London, Ontario, Canada; Western University, London, Ontario, Canada., Lee K; Departments of Obstetrics and Gynaecology and Physiology and Pharmacology, London, Ontario, Canada; Western University, London, Ontario, Canada., Vanin S; Departments of Obstetrics and Gynaecology and Physiology and Pharmacology, London, Ontario, Canada; Western University, London, Ontario, Canada., Laviolette SR; Department of Anatomy and Cell Biology, London, Ontario, Canada; Western University, London, Ontario, Canada., Holloway AC; Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada., Arany E; Department of Pathology and Laboratory Medicine, London, Ontario, Canada; Department of Medicine, London, Ontario, Canada; Western University, London, Ontario, Canada; Children's Health Research Institute, Lawson Health Research Institute, St. Joseph's Health Care, London, Ontario, Canada., Hardy DB; Departments of Obstetrics and Gynaecology and Physiology and Pharmacology, London, Ontario, Canada; Department of Anatomy and Cell Biology, London, Ontario, Canada; Western University, London, Ontario, Canada; Children's Health Research Institute, Lawson Health Research Institute, St. Joseph's Health Care, London, Ontario, Canada. Electronic address: Daniel.Hardy@schulich.uwo.ca.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2020 Jun; Vol. 94, pp. 84-91. Date of Electronic Publication: 2020 Apr 20.
DOI: 10.1016/j.reprotox.2020.04.070
Abstrakt: Recent reports indicate that 7% of pregnant mothers in North America use cannabis. This is concerning given that in utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, causes fetal growth restriction and may alter replication and survival of pancreatic β-cells in the offspring. Accordingly, we hypothesized that maternal exposure to Δ9-THC during pregnancy would impair postnatal glucometabolic health of offspring. To test this hypothesis, pregnant Wistar rats were treated with daily intraperitoneal injections of either 3 mg/kg Δ9-THC or vehicle from gestational day 6 to birth. Offspring were subsequently challenged with glucose and insulin at 5 months of age to assess glucose tolerance and peripheral muscle insulin sensitivity. Female offspring exposed to Δ9-THC in utero were glucose intolerant, associated with blunted insulin response in muscle and increased serum insulin concentration 15 min after glucose challenge. Additionally, pancreata from male and female offspring were harvested at postnatal day 21 and 5 months of age for assessment of endocrine pancreas morphometry by immunostaining. This analysis revealed that gestational exposure to Δ9-THC reduced the density of islets in female, but not male, offspring at postnatal day 21 and 5 months, culminating in reduced β-cell mass at 5 months. These results demonstrate that fetal exposure to Δ9-THC causes female-specific impairments in glucose homeostasis, raising concern regarding the metabolic health of offspring, particularly females, exposed to cannabis in utero.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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