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...

Objective To determine the dose-dependent effect of delta-9-tetrahydrocannabinol (THC) exposure on male testes and reproductive health in a nonhuman primate model. Design Research animal study. Setting Research institute. Animal(s) Adult male rhesus macaques 8–10 years of age (n = 6). Intervention(s) Daily edible THC at medically and recreationally relevant doses. Main Outcome Measure(s) Testicular volume and epididymal head width, serum levels of inhibin B, albumin, total testosterone, prolactin, follicle-stimulating hormone, estradiol, and luteinizing hormone; semen volume; and sperm motility, morphology, and concentration. Result(s) For each 1 mg/7 kg/day increase in THC dosing, there was a marked loss in total bilateral testicular volume of 11.8 cm3 (95% confidence interval [CI]: 8.3–15.4). In total, average bilateral...

Please use this link to access this publication Abstract While the effects of delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, have been studied extensively in the central nervous system, there is limited knowledge about its effects on the female reproductive system. The aim of this study was to assess the effect of THC on the expression and secretion of the angiogenic factor vascular endothelial growth factor (VEGF) in the ovary, and to determine if these effects were mediated by prostaglandins. Spontaneously immortalized rat granulosa cells (SIGCs) were exposed to THC for 24 h. Gene expression, proliferation and TNFα-induced apoptosis were evaluated in the cells and concentrations of VEGF and prostaglandin E2 (PGE2),...

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 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...

Please use this link to access this publication. Abstract Although cannabis use is increasing in general population, their prevalence among young adults is remarkably high. In recent years, their medical use gained a renewed interest. However, it can underline the reputation of cannabis being a harmless drug. Between cannabinoids, uniquely found on the cannabis plant, Δ9-tetrahydrocannabinol (THC) is the well-studied compound. It is responsible for the psychoactive effects via central cannabinoid receptors. Nevertheless, cannabinoids interact with other chemical signalling systems such as the hypothalamic–pituitary–gonadal axis. THC indirectly decreases gonadotropin-releasing hormone (GnRH) secretion by the hypothalamus. The consequences are diverse, and several key hormones are...

Abstract   A total of 1,215 young Danish men aged 18–28 years were recruited between 2008 and 2012 when they attended a compulsory medical examination to determine their fitness for military service. The participants delivered a semen sample, had a blood sample drawn, and underwent a physical examination. They responded to questionnaires including information on marijuana and recreational drug use during the past 3 months (no use, use once per week or less, or use more than once per week). A total of 45% had smoked marijuana within the last 3 months. Regular marijuana smoking more than once per week was associated with a...

Abstract   Objective To evaluate the association between cannabis use and testicular function (as assessed through semen quality and serum hormone levels) in different populations.   Evidence Review Systematic review and meta-analysis of population-based retrospective cohort studies. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Data were pooled using a fixed-effects or random-effects model depending on the heterogeneity of studies included. Pooled risk ratio (RR) of having any sperm abnormality and testosterone, FSH, and LH standardized mean differences among male cannabis users and non-users, and meta-regression analysis according to age and year of publication.   Results Nine studies were...

There has been increasing interest in the role of endocannabinoids as critical modulators of the female reproductive processes. Endocannabinoids are natural ligands of cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. Together with their receptors, enzymes and downstream signaling targets, they form the endocannabinoid system (ECS). While the ECS is known to modulate pain and neurodevelopment, it is also known to impact the female reproductive system where it affects folliculogenesis, oocyte maturation, and ovarian endocrine secretion. In addition, the ECS affects oviductal embryo transport, implantation, uterine decidualization and placentation. There is a complex interplay between the ECS and the hypothalamic-pituitary-ovarian axis, and an intricate crosstalk between...

Endocannabinoids act as a major neuromodulatory system in a variety of physiological and behavioral functions. Three major lines of evidence suggest that the endocannabinoid system interacts with gonadal hormones. First, the endocannabinoid system is implicated in behaviors and physiological functions that are known to be regulated in part by gonadal hormones. Second, receptors and metabolic enzymes of the endocannabinoid system are localized extensively on structures in the hypothalamic-pituitary-gonadal axis. Third, changes in levels of gonadal hormones alter endocannabinoid signaling. Here we reviewed and summarized the current evidence regarding the interaction between the endocannabinoid system and androgens, estrogens, and progesterone. Overall, it appears that bidirectional...