The presence of THC in fetal blood after maternal ingestion and THC and CBD in meconium between 0 and 48 h after delivery indicate these two molecules cross the placenta. The main chemicals present in recreational cannabis are Δ9-tetrahydrocannabinol (THC), which is responsible for the psychoactive effects of marijuana, and cannabidiol (CBD). To date, the effect of this consumption on the human genital tract is unknown. Use of cannabis during pregnancy can induce negative birth outcomes, such as reduced weight, increased risk of prematurity, cognitive deficits, and behavioral and neurocognitive impairment. Cannabis components and their metabolites are well known to cross the placenta barrier. Indeed, phytocannabinoid compounds have been evidenced in 5.3% of newborn meconiums, whereas only 1.7% of the mothers self-reported cannabis use. However, data on pregnant women consumption remain rare and the use of self-reported questionnaires likely underestimates real exposures. Thus, an increase of cannabis use by 3.4–7% of pregnant women in the USA has been reported during this last decade. In the USA, while fetal exposure to tobacco decreases, cannabis use during pregnancy rises along with the enhanced perception that there are no risks with cannabis consumption during pregnancy. In western countries, up to 20% of pregnant women are exposed to cannabis during pregnancy. It is also the commonest recreational drug consumed by pregnant women. Our study is the first to evidence the presence of the ECS in the human fetal testis and to highlight the potential adverse effect of cannabis consumption by pregnant women onto the development of the male gonad.Ĭannabis is the most widely used drug in the world. Depending on the molecules and testis age, highly deleterious effects of phytocannabinoid exposure were observed on testis tissue after 14 days, including Sertoli and germ cell death. Transcriptomic analysis on 72 h-exposed fetal testis explants revealed 187 differentially expressed genes (DEGs), including genes involved in steroid synthesis and toxic substance response. Ex vivo exposure of first trimester testes to CBD, THC, or CBD/THC at 10 −7 to 10 −5 M altered testosterone secretion by Leydig cells, AMH secretion by Sertoli cells, and impacted testicular cell proliferation and viability as early as 72 h post-exposure. We demonstrate the presence in the human fetal testis of two key endocannabinoids, 2-arachidonylglycerol (2-AG) and to a lower level anandamide (AEA), as well as a range of enzymes and receptors for the ECS.
We determined the expression of components of the ECS in the human fetal testis from 6 to 17 developmental weeks and assessed the direct effects of phytocannabinoids Δ9-trans-tetrahydrocannabinol (THC) and cannabidiol (CBD) on the testis morphology and cell functions ex vivo. In this context, we aimed to determine whether cannabis exposure has the potential to directly impact the human fetal testis. The fetal testis, whose endocrine function orchestrates the masculinization of many distant organs, is particularly sensitive to disruption by xenobiotics. Cannabis action is mediated by the endocannabinoid system (ECS), which expression is well established in the brain but unknown in the developing testis. Cannabis consumption by pregnant women continues to increase worldwide, raising concerns about adverse effects on fetal growth and deleterious impacts on the newborn, in connection with evidence of placental transfer of cannabis compound.
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