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Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function and Development in a Rhesus Macaque Model

ABSTRACT: Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function and Development in a Rhesus Macaque Model

PROVIDER: PRJNA892107 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21973219_1.fastq.gz	Fastqsanger.gz
	SRR21973219_2.fastq.gz	Fastqsanger.gz
	SRR21973220_1.fastq.gz	Fastqsanger.gz
	SRR21973220_2.fastq.gz	Fastqsanger.gz
	SRR21973221_1.fastq.gz	Fastqsanger.gz

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Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function

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Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts DNA methylation in a Rhesus Macaque Model [methylation]

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Chronic prenatal delta-9-tetrahydrocannabinol exposure adversely impacts placental function and development in a rhesus macaque model.

Project description: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.

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Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function and Development in a Rhesus Macaque Model

Project description:To investigate the impact of THC exposure on placenta RNA/gene expression Edibles were administered prior to the animal’s daily chow to ensure consumption on an empty stomach and to confirm complete ingestion. Animals were slowly titrated up to 2.5mg/7kg/day of THC using published weight-based medical cannabis acclimation recommendations approximately 4 months prior to undergoing time-mated breeding. Each THC-exposed pregnant animal (n=5) continued to consume a daily edible of 2.5mg/7kg/day throughout pregnancy.

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Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts DNA methylation in a Rhesus Macaque Model [methylation]

Project description:Epigenome-wide profiling of DNAm in samples obtained from 10 rhesus macaques Edibles were administered prior to the animal’s daily chow to ensure consumption on an empty stomach and to confirm complete ingestion. Animals were slowly titrated up to 2.5mg/7kg/day of THC using published weight-based medical cannabis acclimation recommendations approximately 4 months prior to undergoing time-mated breeding. Each THC-exposed pregnant animal (n=5) continued to consume a daily edible of 2.5mg/7kg/day throughout pregnancy.

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Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-01-26 | GSE223826 | GEO

Rhesus macaque (Macaca mulatta) placental transcriptome

Project description:The purpose of the experiment was to compare placental transcriptome of rhesus macaque at approximately 80% completed gestation to human placental transcriptomes.

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Project description:Cannabis is commonly used amongst reproductive age males. Our group and others have shown that chronic delta-9-tetrahydrocannabinol (THC) use adversely impacts male fertility, but less is known about the potential reversibility of these changes. Our study’s objective was to determine if THC discontinuation mitigates THC-associated changes in male reproductive health using a rhesus macaque (RM) model of daily THC edible consumption over a 280-day period (4 spermatogenic cycles). Testicular volume, serum male hormones, semen parameters, sperm DNA fragmentation, seminal fluid proteomics, and whole genome bisulfite sequencing (WGBS) of sperm DNA were assessed at pre-THC, moderate-THC, and heavy-THC dosing, and at 70 and 140 days after THC discontinuation. Chronic THC use resulted in significant testicular atrophy, increased gonadotropins, decreased serum sex steroids, and increased DNA fragmentation. THC discontinuation led to partial recovery of testicular volume, sex steroids and sperm DNA integrity. Seminal fluid proteome analysis revealed differential expression of proteins enriched for processes related to cellular secretion, immune response, and fibrinolysis. WGBS identified significant differential methylation in heavy-THC versus pre-THC sperm, with partial restoration of methylation after discontinuation of THC. Genes associated with differentially methylated regions (DMRs) were enriched for pathways involved in nervous system development and function. This is the first study demonstrating that chronic THC use in RMs adversely impacts male reproductive health, methylation of genes involved in development, and expression of proteins important for male fertility. THC discontinuation improves impacts to male fertility, including partial restoration of THC-associated sperm DMRs in genes important for development.

2023-05-18 | PXD039802 | Pride

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