Oral Concurrent Session 7 - Epidemiology and Quality
Oral Concurrent Sessions
Expedited Sessions
To determine the effect of chronic prenatal cannabis (THC, delta-9-tetrahydrocannabinol) exposure on placental and offspring DNA methylation in rhesus macaques.
Study Design:
Rhesus macaques were divided into control (CON, n=5) and THC-exposed (THC, n=5). All animals consumed a standard chow diet with THC-exposed females receiving a THC edible daily. Animals were titrated to 2.5mg/7kg/day of THC (equivalent to a heavy human medical marijuana dose) over 4 months before time-mated breeding, and were maintained at that THC dose throughout pregnancy. All animals (n=10) underwent c-section delivery at gestational day 155 (term is ~168 days). Placenta, fetal lung, right ventricle of the heart, prefrontal cortex, and cerebellum tissue were collected, flash-frozen, and stored at -80°C for DNA studies. DNA methylation was measured using Illumina Methylation EPIC arrays, filtering for probes validated in rhesus.
Results:
We observed differential methylation following THC exposure in all tissues, with the greatest effect measured in placenta (Fig 1). Differentially methylated region analysis in placenta revealed significant hypermethylation in the MEGF10 gene, previously found to be epigenetically silenced in neuroblastomas. “Nervous system development” was the top gene ontology category enriched among CpGs associated with THC exposure in placenta, lung, and PFC. Remarkably, loci differentially methylated with THC were enriched for known autism spectrum disorder (ASD) genes in all tissues. Seven candidate ASD genes were differentially methylated by THC exposure in all tissues, including AUTS2 which encodes Autism susceptibility candidate 2.
Conclusion:
Prenatal THC exposure alters DNA methylation in placental and fetal tissue at genes involved in neurobehavioral development, with the greatest impact in placenta. Our multi-tissue study demonstrates the utility of our unique rhesus macaque model of in utero THC exposure to study the impact of prenatal cannabis use on fetal development and future health outcomes, and to investigate the underlying molecular mechanisms.
Lyndsey Shorey-Kendrick, PhD (she/her/hers)
Research Professor
Oregon National Primate Research Center
Beaverton, Oregon, United States
Victoria H. Roberts, PhD,BS
Assistant Professor
Oregon National Primate Research Center
Beaverton, Oregon, United States
Elinor Sullivan, PhD
Oregon Health & Science University
Portland, OR, United States
Jose Juanito Terrobias, BS
Oregon National Primate Research Center
Beaverton, OR, United States
Eliot Spindel, MD, PhD
Oregon National Primate Research Center
Beaverton, OR, United States
Jamie Lo, MD, MCR
Associate Professor
Oregon Health & Science University
Portland, OR, United States