Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes

被引：7

作者：

Shorey-Kendrick, Lyndsey E. ^{[1
]}

Roberts, Victoria H. J. ^{[2
]}

D'Mello, Rahul J. ^{[3
]}

Sullivan, Elinor L. ^{[1
,4
,5
]}

Murphy, Susan K. ^{[6
]}

Mccarty, Owen J. T. ^{[7
]}

Schust, Danny J. ^{[6
]}

Hedges, Jason C. ^{[2
,8
]}

Mitchell, A. J. ^{[1
]}

Terrobias, Jose Juanito D. ^{[2
]}

Easley IV, Charles A. ^{[9
]}

Spindel, Eliot R. ^{[1
]}

Lo, Jamie O. ^{[2
,3
]}

机构：

[1] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA

[2] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod & Dev Sci, Beaverton, OR 97006 USA

[3] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Portland, OR 97239 USA

[4] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA

[5] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA

[6] Duke Univ, Dept Obstet & Gynecol, Med Ctr, Durham, NC 27701 USA

[7] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA

[8] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97239 USA

[9] Univ Georgia, Dept Environm Hlth Sci, Coll Publ Hlth, Athens, GA 30602 USA

来源：

CLINICAL EPIGENETICS | 2023年 / 15卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Delta-9-tetrahydrocannabinol (THC); Cannabis; Marijuana; DNA methylation; Prenatal substance use; FETAL-GROWTH RESTRICTION; MARIJUANA USE; CANNABINOID RECEPTORS; EPIGENETIC DYSREGULATION; NONHUMAN-PRIMATES; R PACKAGE; BRAIN; PLACENTA; PREGNANCY; SHANK3;

D O I：

10.1186/s13148-023-01519-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundWith the growing availability of cannabis and the popularization of additional routes of cannabis use beyond smoking, including edibles, the prevalence of cannabis use in pregnancy is rapidly increasing. However, the potential effects of prenatal cannabis use on fetal developmental programming remain unknown.ResultsWe designed this study to determine whether the use of edible cannabis during pregnancy is deleterious to the fetal and placental epigenome. Pregnant rhesus macaques consumed a daily edible containing either delta-9-tetrahydrocannabinol (THC) (2.5 mg/7 kg/day) or placebo. DNA methylation was measured in 5 tissues collected at cesarean delivery (placenta, lung, cerebellum, prefrontal cortex, and right ventricle of the heart) using the Illumina MethylationEPIC platform and filtering for probes previously validated in rhesus macaque. In utero exposure to THC was associated with differential methylation at 581 CpGs, with 573 (98%) identified in placenta. Loci differentially methylated with THC were enriched for candidate autism spectrum disorder (ASD) genes from the Simons Foundation Autism Research Initiative (SFARI) database in all tissues. The placenta demonstrated greatest SFARI gene enrichment, including genes differentially methylated in placentas from a prospective ASD study.ConclusionsOverall, our findings reveal that prenatal THC exposure alters placental and fetal DNA methylation at genes involved in neurobehavioral development that may influence longer-term offspring outcomes. The data from this study add to the limited existing literature to help guide patient counseling and public health polices focused on prenatal cannabis use in the future.

引用

页数：15