Abstract Objective Recreational marijuana use is becoming increasingly widespread. With potential implications for fertility and embryonic development, we set out to evaluate the impact of THC exposure on the pre- and post-implantation embryo through embryonic stem cell proliferation, mitochondrial function and metabolism. Materials and Methods Mouse embryonic stem cells (ESCs) can be differentiated into epiblast-like cells (EpiLCs) using known in vitro methods via growth factors and cytokines. ESCs recapitulate important features of pre-implantation stem cells; EpiLCs model post-implantation features. ESCs and EpiLCs were exposed to a range of Δ9-THC concentrations: 0-100μM over 48 hours. Cell proliferation and viability were assessed via Trypan blue and...

Please use this link to access publication Abstract This review summarizes the most common potential pathways of neurodevelopmental toxicity due to perinatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) that lead to behavioral and other adverse outcomes (AOs). This is Part III in a set of reviews highlighting the animal-derived data considered by California's Developmental and Reproductive Toxicant Identification Committee (DARTIC) in 2019. The Hazard Identification Document (HID) provided to the DARTIC included a summary of human, whole animal, and mechanistic data on the neurodevelopmental toxicity of cannabis smoke and Δ9-THC. The literature search for mechanistic data has been updated through 2020. We focus on mechanistic pathways...

Abstract 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...

Abstract As cannabis use during pregnancy increases, it is important to understand its effects on the developing fetus. Particularly, the long-term effects of its psychoactive component, delta-9-tetrahydrocannabinol (THC), on the offspring’s reproductive health are not fully understood. This study examined the impact of gestational THC exposure on the miRNA profile in adult rat ovaries and the possible consequences on ovarian health. Prenatal THC exposure resulted in the differential expression of 12 out of 420 evaluated miRNAs. From the differentially expressed miRNAs, miR-122-5p, which is highly conserved among species, was the only upregulated target and had the greatest fold change. The upregulation of miR-122-5p and...

Please use this link to access this publication Abstract Background Cannabis 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. Methods Rat 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...

Abstract Despite increased prevalence of maternal cannabis use, little is understood regarding potential long-term effects of prenatal cannabis exposure (PCE) on neurodevelopmental outcomes. While neurodevelopmental cannabis exposure increases the risk of developing affective/mood disorders in adulthood, the precise neuropathophysiological mechanisms in male and female offspring are largely unknown. Given the interconnectivity of the endocannabinoid (ECb) system and the brain’s fatty acid pathways, we hypothesized that prenatal exposure to Δ9-tetrahydrocannabinol (THC) may dysregulate fetal neurodevelopment through alterations of fatty-acid dependent synaptic and neuronal function in the mesolimbic system. To investigate this, pregnant Wistar rats were exposed to vehicle or THC (3 mg/kg) from gestational day (GD)7...

Abstract Pre and perinatal administration of Tetrahydrocannabinol (THC) in rodents and their offspring has many effects that have been studied using different methods that have not been integrated using quantitative methods. The effect of THC administration on behavior can be better understood by meta-analytic techniques. We examined whether there is an overall effect on the behavior of the offspring when THC is administered to mothers. Eligibility criteria included experiments using an experimental design with a control group without THC, in which THC is administered to mothers during pregnancy and lactation in rodents, and in which at least one type of behavioral (locomotor, emotional or...

Abstract Cannabidiol (CBD), one of the main components of cannabis, is generally considered safe. CBD crosses the placenta and its use during pregnancy is steadily increasing, the impact of gestational CBD’s effects on prenatal life and neurodevelopment are poorly understood. Here, we combined behavioral approaches and deep learning analysis to assess the sex-dependent neonatal behavior of CBD exposed progeny. Gestating C57BL6/J dams were exposed daily with vehicle or CBD (3 mg/Kg, s.c.), from gestational day 5 to 18. Body weight, pup ultrasound vocalizations (USVs, PND 10) and homing behavior (PND 13) were quantified in the progeny. Thus, male (but not female) pups from CBD-treated dams...

Abstract Introduction: There is widespread acceptance of cannabis for medical or recreational use across the society, including pregnant women. Concerningly, numerous studies find that the developing central nervous system (CNS) is vulnerable to the detrimental effects of Δ9-tetrahydrocannabinol (THC). In contrast, almost nothing on the consequences of perinatal cannabidiol (CBD) exposure. In this study, we used mice to investigate the adult impact of perinatal cannabinoid exposure (PCE) with THC, CBD, or a 1:1 ratio of THC and CBD on behaviors. Furthermore, the lasting impact of PCE on fluoxetine sensitivity in the forced swim test (FST) was evaluated to probe neurochemical pathways interacting with the endocannabinoid...

Please use this link to access this publication. Abstract Cannabis is the most commonly used federally illegal drug in the United States and the world, especially among people of reproductive age. In addition, the potency of cannabis products has increased significantly in the past decade. This is concerning because the available evidence suggests an adverse effect of cannabis exposure on male and female reproductive health. Exposure to cannabinoids may have differential impacts on female reproductive health across a woman’s lifespan, from preconception to pregnancy, throughout lactation, and during menopause. Moreover, cannabis use has been associated with adverse effects on fetal outcomes and longer-term offspring health and developmental trajectories. Despite the prevalence of cannabis use, there is limited...