PB1526 - Impact of maternal cannabis use on fetal vascularized tissue development

Background: Cannabis use is rapidly rising among individuals of reproductive age; there remains a paucity of evidence on the safety and long-term patho-physiological effects of cannabis on reproductive biology. Limited existing studies suggest that prenatal cannabis exposure may lead to impaired fetal neurodevelopment; however, the effects on other highly vascularized fetal tissues, including skeletal muscle, have not been explored.

Aims: To address this research gap, we used a translational, rhesus macaque model to examine the impact of chronic maternal delta-9-tetrahydrocannabinol (THC, the main active component of cannabis) exposure on fetal vascular and musculoskeletal development.

Methods: Female rhesus macaques (n=10) were divided into 2 groups, control (n=5) and THC-exposed (n=5). THC-exposed animals received a daily edible with 2.5mg/7kg/day of THC starting preconception and maintained throughout gestation. Animals underwent time-mated breeding and were delivered by cesarean delivery at gestational day 155 (term is ~168 days). All fetuses underwent necropsy with fetal skeletal muscle tissue collection. RNA was isolated from the skeletal muscle and evaluated for differential gene expression using the Nanostring nCounter neuroinflammatory panel comprised of ~700 genes.

Results: We identified multiple differentially expressed (≥1.5-fold) genes between the THC-exposed and control animals, that are associated with vascular biology and inflammation. Specifically, CCL4, which plays a role in calcium mobilization in vascular smooth muscle cells, was downregulated by 3.7-fold. Additionally, ERG-1 which has been shown to induce vascular inflammation, is upregulated in the THC exposure group by 1.7-fold. The genes CNN2, GJA1, PTGER3, and PTGER4 all contribute to inflammatory signaling and THC exposure led to upregulation by 1.6, 1.6, 2.3, and 1.9-fold, respectively. Studies are currently underway to evaluate the histomorphology of the vascular networks present in these tissues.

Conclusion(s): Our study suggests that prenatal THC exposure may adversely impact vascular biology and inflammatory signaling in rhesus macaques.