Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy.
Mech Ageing Dev. 2023 Jul;213:111840. doi: 10.1016/j.mad.2023.111840. Epub 2023 Jun 28.
Cannabis use during pregnancy is increasing in the last few years potentially because of decreased perception of the risk of harm. Regardless, recent evidence demonstrated that prenatal cannabis exposure is associated with adverse outcomes. To date there is limited evidence of the impact of cannabis exposure during pregnancy on the reproductive health of the offspring. The biological effects of cannabis are mediated by two cannabinoid receptors, CB and CB. We previously demonstrated that CB is highly expressed in mouse male and female fetal germ cells. In this study, we investigated the effects of prenatal exposure to a selective CB agonist, JWH-133, on the long-term reproductive health of male and female offspring and on the involved molecular epigenetic mechanisms. Notably, we focused on epigenetic histone modifications that can silence or activate gene expression, playing a pivotal role in cell differentiation. We reported that prenatal activation of CB has a sex-specific impact on germ cell development of the offspring. In male it determines a delay of germ cell differentiation coinciding with an enrichment of H3K27me3, while in female it causes a reduction of the follicles number through an increased apoptotic process not linked to modified H3K27me3 level.
近年来，孕妇吸食大麻的现象有所增加，这可能是因为人们对其危害的认知有所降低。尽管如此，最近的证据表明，产前大麻暴露与不良后果有关。迄今为止，关于孕妇吸食大麻对后代生殖健康影响的证据有限。大麻的生物学效应是由两种大麻素受体 CB 和 CB 介导的。我们之前的研究表明，CB 在雄性和雌性胎生生殖细胞中高度表达。在这项研究中，我们研究了产前暴露于选择性 CB 激动剂 JWH-133 对雄性和雌性后代长期生殖健康的影响及其涉及的分子表观遗传机制。值得注意的是，我们专注于表观遗传组蛋白修饰，这些修饰可以沉默或激活基因表达，在细胞分化中发挥关键作用。我们报告称，产前 CB 的激活对后代生殖细胞的发育具有性别特异性影响。在雄性中，它导致生殖细胞分化延迟，同时 H3K27me3 富集；而在雌性中，它通过增加与 H3K27me3 水平改变无关的凋亡过程导致卵泡数量减少。
