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孕期口服大麻对小鼠母体螺旋动脉重塑、胎儿生长及子代行为的影响。

The impact of oral cannabis consumption during pregnancy on maternal spiral artery remodelling, fetal growth and offspring behaviour in mice.

作者信息

Ritchie Tyrah M, Feng Emily, Vahedi Fatemeh, Ermolina Sofya, Bellissimo Christian J, De Jong Erica, Portillo Ana L, Poznanski Sophie M, Chan Lauren, Ettehadieh Sara M, Sloboda Deborah M, Bowdish Dawn M E, Ashkar Ali A

机构信息

Department of Medicine, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada.

Department of Medicine, McMaster University, Hamilton, ON, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada.

出版信息

EBioMedicine. 2025 Apr;114:105572. doi: 10.1016/j.ebiom.2025.105572. Epub 2025 Feb 5.

DOI:10.1016/j.ebiom.2025.105572
PMID:39915201
Abstract

BACKGROUND

The use of cannabis during pregnancy is rising following its widespread legalization. Cannabidiol (CBD) is gaining popularity due to the public perception that it is safer than the psychoactive cannabis component Δ9-tetrahydrocannabinol (THC). However, while evidence underpins the harm of THC and cannabis smoke on fetal development, there is minimal research on the safety of CBD and oral cannabis. The current study aims to decipher the safety of oral CBD and THC use during pregnancy.

METHODS

Using a mouse model, we directly compared the effects of oral CBD and THC oil exposure (20 mg/kg body weight) from early to mid-gestation on implantation site remodelling and fetal growth. We examined offspring behaviour and metabolic activity using both traditional and automated cage systems. Lastly, using human and mouse immune cells we assessed how CBD and THC influence angiogenic factor production.

FINDINGS

We observed impaired maternal spiral artery remodelling in cannabis exposed mice and found that CBD and THC disrupt immune cell angiogenic factor production. Oral consumption of THC or CBD oil also resulted in significant fetal growth impairment and led to long-lasting sex-dependent consequences as male offspring exhibited altered aggression and metabolic activity while females had impaired spatial learning.

INTERPRETATION

Our results show that oral consumption of either CBD or THC oil during pregnancy in mice results in harm to the developing fetus and causes behavioural changes after birth.

FUNDING

The Michael G. DeGroote Centre for Medicinal Cancer Research, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation.

摘要

背景

随着大麻的广泛合法化,孕期使用大麻的情况正在增加。大麻二酚(CBD)因公众认为其比具有精神活性的大麻成分Δ9-四氢大麻酚(THC)更安全而越来越受欢迎。然而,虽然有证据支持THC和大麻烟雾对胎儿发育的危害,但关于CBD和口服大麻安全性的研究却很少。本研究旨在解读孕期口服CBD和THC的安全性。

方法

我们使用小鼠模型,直接比较了从妊娠早期到中期口服CBD和THC油(20毫克/千克体重)对植入部位重塑和胎儿生长的影响。我们使用传统和自动化笼养系统检查了后代的行为和代谢活动。最后,我们使用人和小鼠免疫细胞评估了CBD和THC如何影响血管生成因子的产生。

研究结果

我们观察到暴露于大麻的小鼠母体螺旋动脉重塑受损,并发现CBD和THC会干扰免疫细胞血管生成因子的产生。口服THC或CBD油还导致了显著的胎儿生长受损,并导致了长期的性别依赖性后果,因为雄性后代表现出攻击性和代谢活动的改变,而雌性后代的空间学习能力受损。

解读

我们的结果表明,小鼠孕期口服CBD或THC油会对发育中的胎儿造成伤害,并导致出生后的行为变化。

资金来源

迈克尔·G·德格罗特医学癌症研究中心、加拿大卫生研究院和加拿大创新基金会。

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