Rokeby Abbey C E, Natale Bryony V, Natale David R C
Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Department of Obstetrics and Gynaecology, Queen's University, Kingston, ON, Canada.
Placenta. 2023 Apr;135:51-61. doi: 10.1016/j.placenta.2023.03.002. Epub 2023 Mar 10.
Cannabis use during pregnancy is increasing. The improvement of pregnancy-related symptoms including morning sickness and management of mood and stress are among the most reported reasons for its use. Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the most abundant cannabinoids found within the cannabis flower. The concentration of these components has drastically increased in the past 20 years. Additionally, many edibles contain only one cannabinoid and are marketed to achieve a specific goal, meaning there are an increasing number of pregnancies that are exposed to isolated cannabinoids. Both Δ9-THC and CBD cross the placenta and can impact the fetus directly, but the receptors through which cannabinoids act are also expressed throughout the placenta, suggesting that the effects of in-utero cannabinoid exposure may include indirect effects from the placenta. In-utero cannabis research focuses on short and long-term fetal health and development; however, these studies include little to no placenta analysis. Prenatal cannabinoid exposure is linked to small for gestational age and fetal growth-restricted babies. Compromised placental development is also associated with fetal growth restriction and the few studies (clinical and animal models) that included placental analysis, identify changes in placental vasculature and function in these cannabinoid-exposed pregnancies. In vitro studies further support cannabinoid impact on cell function in the different populations that comprise the placenta. In this article, we aim to summarize how phytocannabinoids can impact placental development and function. Specifically, the cannabinoids and their actions at the different receptors are described, with receptor localization throughout the human and murine placenta discussed. Findings from studies that included placental analysis and how cannabinoid signaling may modulate critical developmental processing including cell proliferation, angiogenesis and migration are described. Considering the current research, prenatal cannabinoid exposure may significantly impact placental development, and, as such, identifying windows of placental vulnerability for each cannabinoid will be critical to elucidate the etiology of fetal outcome studies.
孕期使用大麻的情况正在增加。改善与妊娠相关的症状，包括孕吐以及情绪和压力管理，是使用大麻最常被提及的原因。Δ9-四氢大麻酚（Δ9-THC）和大麻二酚（CBD）是大麻花朵中含量最丰富的大麻素。在过去20年中，这些成分的浓度急剧增加。此外，许多可食用大麻制品仅含有一种大麻素，并以实现特定目标进行销售，这意味着越来越多的孕妇会接触到单一的大麻素。Δ9-THC和CBD均可穿过胎盘并直接影响胎儿，但大麻素作用的受体在整个胎盘中也有表达，这表明子宫内大麻素暴露的影响可能包括来自胎盘的间接影响。子宫内大麻研究主要关注胎儿的短期和长期健康与发育；然而，这些研究几乎没有对胎盘进行分析。产前大麻素暴露与小于胎龄儿和胎儿生长受限有关。胎盘发育受损也与胎儿生长受限有关，少数包括胎盘分析的研究（临床和动物模型）发现，在这些暴露于大麻素的妊娠中，胎盘血管系统和功能发生了变化。体外研究进一步支持大麻素对构成胎盘的不同细胞群体功能的影响。在本文中，我们旨在总结植物大麻素如何影响胎盘发育和功能。具体而言，描述了大麻素及其在不同受体上的作用，并讨论了其在人和小鼠胎盘各处的受体定位。介绍了包括胎盘分析的研究结果，以及大麻素信号传导如何调节包括细胞增殖、血管生成和迁移在内的关键发育过程。考虑到当前的研究，产前大麻素暴露可能会显著影响胎盘发育，因此，确定每种大麻素的胎盘脆弱期对于阐明胎儿结局研究的病因至关重要。
