Cannabis use may occur during pregnancy to alleviate symptoms of nausea, anxiety, and stress. However, fetal exposure to cannabinoids, such as THC and CBD, poses potential risks to neurodevelopment and long-term health outcomes. The endocannabinoid system (ECS) is involved in neurodevelopment and gastrointestinal (GI) homeostasis and responds to exogenous cannabinoids. This study aimed to investigate both the baseline development of the ECS in the GI tract and the effects of prenatal cannabis exposure on the development of gut-brain axis components and the ECS. Samples from outbred mice were collected at a set of developmentally important time points, ranging from embryonic day 14 to postnatal day 21. The localization of cannabinoid receptor 1 (CB1) expression was examined in the fetal and postnatal small intestine, and mRNA analysis was performed to evaluate changes in gene expression. Under normal conditions, components of the ECS display developmental regulation in the GI tract. A subset of pregnant mice was exposed to cannabis smoke daily, using a strain of cannabis containing high concentrations of THC, simulating ‘real world’ cannabis use. Exposure to cannabis prenatally revealed significant changes in biometric outcomes, and in the transcription of genes associated with the ECS, ENS development, barrier function, and serotonin signaling pathways. In addition, the onset of ambulation was delayed. These findings provide valuable insights into the developmental regulation of ECS during the prenatal period and highlight the potential risks associated with prenatal cannabis exposure, particularly in terms of gut-brain axis development. Further research is required to better understand the underlying mechanisms. / Thesis / Master of Science (MSc) / There have been growing reports of cannabis consumption during pregnancy, to relieve nausea, anxiety, and stress. However, compounds in cannabis, like THC and CBD, can pose risks to the baby's development and long-term health. This project studied how cannabis use during pregnancy affects gastrointestinal (GI) development, and communication between the GI system and the brain. The endocannabinoid system (ECS) plays a role in regulating the normal functioning of the GI tract and is influenced by cannabis compounds. By exposing pregnant mice to cannabis smoke, we observed significant changes in gene expression in the fetal intestine relating to the GI nervous system, the strength of the gut barrier, and various molecular signalling pathways. In addition, prenatally exposed mice had delayed walking ability. These findings highlight the potential risks of cannabis use during pregnancy on gut-brain axis development. Further research is needed to understand the mechanisms causing these disruptions.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/28971 |
| Date | January 2023 |
| Creators | Sunil, Maria |
| Contributors | Ratcliffe, Elyanne, Medical Sciences (Division of Physiology/Pharmacology) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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