Related Experiment Video
Updated: Jun 19, 2026
Preclinical Model of Prenatal Delta-9-Tetrahydrocannabinol Exposure to Assess Its Impact on Neurodevelopmental Outcomes
Published on: February 28, 2025
Prenatal cannabis use is associated with altered miRNA and protein expression in the developing human brain
Lierni Ugartemendia1, Baharan Fekry1, Robert Suchting2
1Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, TX, USA.
Background:
Cannabis is widely used during pregnancy, increasing with cannabis legalization, and has been associated with altered neurodevelopment, yet the precise molecular mechanisms remain poorly understood.
Aims:
To assess whether utilizing fetal central nervous system-derived extracellular vesicles (fCNSEVs) isolated from maternal blood reflects cannabis-associated changes in the fetal brain.
Methods:
In a matched case-control study, maternal plasma (to isolate fCNSEVs) and paired fetal cortical tissue (9-18 weeks' gestation) from pregnancies exposed or unexposed to cannabis were collected. We quantified protein (CB1R, D2R) and miRNA expression (using µ-parafloTM microarray). Selected miRNAs were validated by qPCR. Bayesian Generalized Linear Models were used to assess exposure-group by sex effects.
Results:
Maternal cannabis use was associated with altered CB1R and D2R levels in the brain with opposite directional changes in fCNSEVs. 21 miRNAs were differentially expressed: 14 downregulated and 6 upregulated, following a sex-dependent pattern (males>>females), while miR-216a-5p follows the opposite pattern (females>>males). We confirmed concordant miRNA changes in fetal brain and fCNSEVs. Many of the identified molecules are associated with pathways linked to adverse neurodevelopmental outcomes.
Conclusions:
Our data suggest that fCNSEV-based assays may provide the ability to monitor fetal brain effects of maternal cannabis in ongoing pregnancies in clinical cohorts. A critical next step is to determine if alterations in fCNSEV protein and miRNA markers predict changes in fetal brain connectivity and neurodevelopment measures of executive function.
