Similar Datasets
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.
| S-EPMC9691736 | biostudies-literature
Project description:Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function
| PRJNA928465 | ENA
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.
2022-10-24 | GSE216112 | GEO
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.
2023-09-11 | GSE223825 | GEO
Project description:Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts Placental Function and Development in a Rhesus Macaque Model
| PRJNA892107 | ENA
Project description:Chronic Prenatal Delta-9-tetrahydrocannabinol Exposure Adversely Impacts DNA methylation in a Rhesus Macaque Model [methylation]
| PRJNA928470 | ENA
Project description:Alterations of long-term synaptic plasticity have been proposed to participate in the development of addiction. To preserve synaptic functions, homeostatic processes must be engaged after exposure to abused drugs. At the mouse cortico-accumbens synapses, a single in vivo injection of Delta9-tetrahydrocannabinol (THC) suppresses endocannabinoid-mediated long-term depression. Using biochemical and electrophysiological approaches, we now report that 1 week of repeated in vivo THC treatment reduces the coupling efficiency of cannabinoid CB1 receptors (CB1Rs) to G(i/o) transduction proteins, as well as CB1R-mediated inhibition of excitatory synaptic transmission at the excitatory synapses between the prefrontal cortex and the nucleus accumbens (NAc). Nonetheless, we found that cortico-accumbens synapses unexpectedly express normal long-term depression because of a reversible switch in its underlying mechanisms. The present data show that, in THC-treated mice, long-term depression is expressed because a presynaptic mGluR2/3 (metabotropic glutamate receptor 2/3)-dependent mechanism replaces the impaired endocannabinoid system. Thus, in the NAc, a novel form of presynaptic homeostasis rescues synaptic plasticity from THC-induced deficits.
| S-EPMC6726043 | biostudies-literature
Project description:BackgroundCannabis remains one of the most widely abused drugs during pregnancy. In utero exposure to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC), can result in long-term neuropsychiatric risk for the progeny. This study investigated epigenetic signatures underlying these enduring consequences.MethodsRat dams were exposed daily to THC (0.15 mg/kg) during pregnancy, and adult male offspring were examined for reward and depressive-like behavioral endophenotypes. Using unbiased sequencing approaches, we explored transcriptional and epigenetic profiles in the nucleus accumbens (NAc), a brain area central to reward and emotional processing. An in vitro CRISPR (clustered regularly interspaced short palindromic repeats) activation model coupled with RNA sequencing was also applied to study specific consequences of epigenetic dysregulation, and altered molecular signatures were compared with human major depressive disorder transcriptome datasets.ResultsPrenatal THC exposure induced increased motivation for food, heightened learned helplessness and anhedonia, and altered stress sensitivity. We identified a robust increase specific to males in the expression of Kmt2a (histone-lysine N-methyltransferase 2A) that targets H3K4 (lysine 4 on histone H3) in cellular chromatin. Normalizing Kmt2a in the NAc rescued the motivational phenotype of prenatally THC-exposed animals. Comparison of RNA- and H3K4me3-sequencing datasets from the NAc of rat offspring with the in vitro model of Kmt2a upregulation revealed overlapping, significant disturbances in pathways that mediate synaptic plasticity. Similar transcriptional alterations were detected in human major depressive disorder.ConclusionsThese studies provide direct evidence for the persistent effects of prenatal cannabis exposure on transcriptional and epigenetic deviations in the NAc via Kmt2a dysregulation and associated psychiatric vulnerability.
| S-EPMC8957623 | biostudies-literature
Project description:Prenatal cannabis use is a significant problem and poses important health risks for the developing fetus. The molecular mechanisms underlying these changes are not fully elucidated but are thought to be attributed to delta-9-tetrahydrocannabinol (THC), the main bioactive constituent of cannabis. It has been reported that THC may target the mitochondria in several tissue types, including placental tissue and trophoblast cell lines, and alter their function. In the present study, in response to 48-h THC treatment of the human extravillous trophoblast cell line HTR8/SVneo, we demonstrate that cell proliferation and invasion are significantly reduced. We further demonstrate THC-treatment elevated levels of cellular reactive oxygen species and markers of lipid damage. This was accompanied by evidence of increased mitochondrial fission. We also observed increased expression of cellular stress markers, HSP70 and HSP60, following exposure to THC. These effects were coincident with reduced mitochondrial respiratory function and a decrease in mitochondrial membrane potential. Taken together, our results suggest that THC can induce mitochondrial dysfunction and reduce trophoblast invasion; outcomes that have been previously linked to poor placentation. We also demonstrate that these changes in HTR8/SVneo biology may be variably mediated by cannabinoid receptors CB1 and CB2.
| S-EPMC7889882 | biostudies-literature
Project description:Phthalates are endocrine-disrupting chemicals that can cross the placenta and affect the fetal epigenome. Among various epigenetic regulators of gene expression, long noncoding RNAs (lncRNAs) are important players that may also be involved in the manifestation of endocrine-disrupting chemical toxicity. We sought to explore the association between maternal urinary phthalate metabolite concentrations and lncRNA expression in human placenta to better understand potential mechanisms through which lncRNAs participate in mediating phthalate toxicity. Ten patients with uncomplicated dichorionic diamniotic twin pregnancies at term were included in this study. Urinary (n = 10) and placenta samples (n = 20) were collected for all participants. Urinary samples were analyzed for 15 phthalate metabolites and 2 phthalate alternative metabolites. Real-time PCR arrays were used to identify and quantify 87 lncRNAs from the placental samples. We tested the Spearman correlation matrix to compare prenatal phthalate measures against placental lncRNA levels. lncRNA levels showed large variations across samples, with no significant differences in lncRNA expression within twin pairs. Mono-(carboxynonyl) phthalate demonstrated consistently strong correlations with most lncRNAs. The strongest correlation was observed between mono-hydroxyisobutyl phthalate and LOC91450 (Rspearman = 0.88, p < .001). This correlation remained significant after Bonferroni adjustment. Other strong correlations were observed between mono-isobutyl phthalate, DPP10 and HOTTIP (Rspearman = -0.91, p < .001). AIRN, DACT3.AS1, DLX6, DPP10, HOTTIP, LOC143666, and LOC91450 were strongly correlated with the greatest number of phthalate metabolites. Further studies are needed to validate these results and understand if the altered expression of lncRNAs in human placenta has clinical significance.
| S-EPMC5917778 | biostudies-other