Prenatal delta-9-tetrahydrocannabinol Exposure is Associated with Altered Fetal Neurodevelopment in Rhesus Macaques
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ABSTRACT: Cannabis use during pregnancy is associated with adverse neurodevelopmental outcomes. However, the underlying mechanisms and effects of cannabis on fetal development are relatively unknown. We determined the impact of chronic delta-9-tetrahydrocannabinol (THC, cannabis’s main psychoactive component) exposure on fetal development in a rhesus macaque model using advanced imaging combined with molecular and tissue studies. Animals were divided into control (n=5) or THC-exposed (n=5) groups, which received a daily THC edible pre-conception and throughout pregnancy. Animals underwent fetal brain T2-weighted MRI at gestational days 85 (G85), G110, G135 and G155 (term is ~G168) to assess brain development. All animals underwent cesarean delivery with fetal cerebral spinal fluid (CSF) and brain collection at G155 for microRNA (miRNA) and histologic analysis. THC exposure did not demonstrate any fetal brain volumetric changes. However, histological findings in THC-exposed brains suggested brain dysregulation that may have long-term developmental implications. We identified two extracellular-vesicle-associated miRNAs (mir-448 and mir-199a-3p) with>2-fold change in CSF with maternal THC use. Amniotic fluid (AF) was collected at the 4 gestational ages (GA) and relative protein abundance changes measured with isobaric labeling quantitative proteomics. Changes in AF were observed across the GAs and in response to THC-treatment.
INSTRUMENT(S):
ORGANISM(S): Macaca Mulatta (rhesus Macaque)
TISSUE(S): Amniotic Fluid
SUBMITTER:
Phillip Wilmarth
LAB HEAD: Jamie Lo, MD MCR
PROVIDER: PXD042447 | Pride | 2025-07-18
REPOSITORIES: Pride
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