Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes
Abstract Background With 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 development...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-07-01
|
| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-023-01519-4 |
| _version_ | 1827905461258551296 |
|---|---|
| author | Lyndsey E. Shorey-Kendrick Victoria H. J. Roberts Rahul J. D’Mello Elinor L. Sullivan Susan K. Murphy Owen J. T. Mccarty Danny J. Schust Jason C. Hedges A. J. Mitchell Jose Juanito D. Terrobias Charles A. Easley Eliot R. Spindel Jamie O. Lo |
| author_facet | Lyndsey E. Shorey-Kendrick Victoria H. J. Roberts Rahul J. D’Mello Elinor L. Sullivan Susan K. Murphy Owen J. T. Mccarty Danny J. Schust Jason C. Hedges A. J. Mitchell Jose Juanito D. Terrobias Charles A. Easley Eliot R. Spindel Jamie O. Lo |
| author_sort | Lyndsey E. Shorey-Kendrick |
| collection | DOAJ |
| description | Abstract Background With 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. Results We 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. Conclusions Overall, 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. |
| first_indexed | 2024-03-13T00:41:58Z |
| format | Article |
| id | doaj.art-d2959dbd43f84fb09f1906fd4819661d |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-03-13T00:41:58Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-d2959dbd43f84fb09f1906fd4819661d2023-07-09T11:17:03ZengBMCClinical Epigenetics1868-70832023-07-0115111510.1186/s13148-023-01519-4Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genesLyndsey E. Shorey-Kendrick0Victoria H. J. Roberts1Rahul J. D’Mello2Elinor L. Sullivan3Susan K. Murphy4Owen J. T. Mccarty5Danny J. Schust6Jason C. Hedges7A. J. Mitchell8Jose Juanito D. Terrobias9Charles A. Easley10Eliot R. Spindel11Jamie O. Lo12Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science UniversityDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science UniversityDepartment of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Oregon Health and Science UniversityDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science UniversityDepartment of Obstetrics and Gynecology, Duke University Medical CenterDepartment of Biomedical Engineering, Oregon Health and Science UniversityDepartment of Obstetrics and Gynecology, Duke University Medical CenterDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science UniversityDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science UniversityDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science UniversityDepartment of Environmental Health Science, University of Georgia College of Public HealthDivision of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science UniversityDivision of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science UniversityAbstract Background With 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. Results We 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. Conclusions Overall, 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.https://doi.org/10.1186/s13148-023-01519-4Delta-9-tetrahydrocannabinol (THC)CannabisMarijuanaDNA methylationPrenatal substance use |
| spellingShingle | Lyndsey E. Shorey-Kendrick Victoria H. J. Roberts Rahul J. D’Mello Elinor L. Sullivan Susan K. Murphy Owen J. T. Mccarty Danny J. Schust Jason C. Hedges A. J. Mitchell Jose Juanito D. Terrobias Charles A. Easley Eliot R. Spindel Jamie O. Lo Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes Clinical Epigenetics Delta-9-tetrahydrocannabinol (THC) Cannabis Marijuana DNA methylation Prenatal substance use |
| title | Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes |
| title_full | Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes |
| title_fullStr | Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes |
| title_full_unstemmed | Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes |
| title_short | Prenatal delta-9-tetrahydrocannabinol exposure is associated with changes in rhesus macaque DNA methylation enriched for autism genes |
| title_sort | prenatal delta 9 tetrahydrocannabinol exposure is associated with changes in rhesus macaque dna methylation enriched for autism genes |
| topic | Delta-9-tetrahydrocannabinol (THC) Cannabis Marijuana DNA methylation Prenatal substance use |
| url | https://doi.org/10.1186/s13148-023-01519-4 |
| work_keys_str_mv | AT lyndseyeshoreykendrick prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT victoriahjroberts prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT rahuljdmello prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT elinorlsullivan prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT susankmurphy prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT owenjtmccarty prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT dannyjschust prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT jasonchedges prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT ajmitchell prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT josejuanitodterrobias prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT charlesaeasley prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT eliotrspindel prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes AT jamieolo prenataldelta9tetrahydrocannabinolexposureisassociatedwithchangesinrhesusmacaquednamethylationenrichedforautismgenes |