TY - JOUR
T1 - Chronic prenatal delta-9-tetrahydrocannabinol exposure adversely impacts placental function and development in a rhesus macaque model
AU - Roberts, Victoria
AU - Schabel, Matthias C.
AU - Boniface, Emily R.
AU - D’Mello, Rahul J.
AU - Morgan, Terry
AU - Terrobias, Juanito Jose D.
AU - Graham, Jason A.
AU - Borgelt, Laura M.
AU - Grant, Kathleen (Kathy)
AU - Sullivan, Elinor
AU - Lo, Jamie
N1 - Funding Information:
This work was funded by NIH/NICHD grant R03 HD097116, NIH/NICHD RSDP K12 HD000849, NIH P51-OD-011092, March of Dimes, Silver Family Innovation Award.
Funding Information:
We would like to thank the veterinary and husbandry staff at ONPRC who provided excellent care for the animals used in this study, in particular Dr. Lauren Drew Martin, Dr. Heather Sidener, Travis Hodge, Mike Reusz, and Trent Crowley. Additionally, we would like to thank the Integrated Genomics Laboratory and Gene Profiling Shared Resource, and the Bioanalytical Shared Resource/Pharmacokinetics Core at OHSU. National Institute of Drug Abuse (NIDA) Drug Supply Program.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Cannabis use in pregnancy is associated with adverse perinatal outcomes, which are likely mediated by the placenta. However, the underlying mechanisms and specific vasoactive effects of cannabis on the placenta are unknown. Our objective was to determine the impact of chronic prenatal delta-tetrahydrocannabinol (THC, main psychoactive component of cannabis) exposure on placental function and development in a rhesus macaque model using advanced imaging. Animals were divided into two groups, control (CON, n = 5) and THC-exposed (THC, n = 5). THC-exposed animals received a THC edible daily pre-conception and throughout pregnancy. Animals underwent serial ultrasound and MRI at gestational days 85 (G85), G110, G135 and G155 (full term is ~ G168). Animals underwent cesarean delivery and placental collection at G155 for histologic and RNA-Seq analysis. THC-exposed pregnancies had significantly decreased amniotic fluid volume (p < 0.001), placental perfusion (p < 0.05), and fetal oxygen availability (p < 0.05), all indicators of placental insufficiency. Placental histological analysis demonstrated evidence of ischemic injury with microinfarctions present in THC-exposed animals only. Bulk RNA-seq demonstrated that THC alters the placental transcriptome and pathway analysis suggests dysregulated vasculature development and angiogenesis pathways. The longer-term consequences of these adverse placental findings are unknown, but they suggest that use of THC during pregnancy may deleteriously impact offspring development.
AB - Cannabis use in pregnancy is associated with adverse perinatal outcomes, which are likely mediated by the placenta. However, the underlying mechanisms and specific vasoactive effects of cannabis on the placenta are unknown. Our objective was to determine the impact of chronic prenatal delta-tetrahydrocannabinol (THC, main psychoactive component of cannabis) exposure on placental function and development in a rhesus macaque model using advanced imaging. Animals were divided into two groups, control (CON, n = 5) and THC-exposed (THC, n = 5). THC-exposed animals received a THC edible daily pre-conception and throughout pregnancy. Animals underwent serial ultrasound and MRI at gestational days 85 (G85), G110, G135 and G155 (full term is ~ G168). Animals underwent cesarean delivery and placental collection at G155 for histologic and RNA-Seq analysis. THC-exposed pregnancies had significantly decreased amniotic fluid volume (p < 0.001), placental perfusion (p < 0.05), and fetal oxygen availability (p < 0.05), all indicators of placental insufficiency. Placental histological analysis demonstrated evidence of ischemic injury with microinfarctions present in THC-exposed animals only. Bulk RNA-seq demonstrated that THC alters the placental transcriptome and pathway analysis suggests dysregulated vasculature development and angiogenesis pathways. The longer-term consequences of these adverse placental findings are unknown, but they suggest that use of THC during pregnancy may deleteriously impact offspring development.
UR - http://www.scopus.com/inward/record.url?scp=85142517904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85142517904&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-24401-4
DO - 10.1038/s41598-022-24401-4
M3 - Article
C2 - 36424495
AN - SCOPUS:85142517904
VL - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 20260
ER -