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大麻素表观遗传学对人类发育的影响:对 Murphy 等人的思考。'大麻素暴露与大鼠和人精子中 DNA 甲基化的改变'表观遗传学 2018; 13: 1208-1221。

Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. 'cannabinoid exposure and altered DNA methylation in rat and human sperm' epigenetics 2018; 13: 1208-1221.

机构信息

Division of Psychiatry, University of Western Australia , Crawley , Western Australia Australia.

School of Medical and Health Sciences, Edith Cowan University , Joondalup , Western Australia , Australia.

出版信息

Epigenetics. 2019 Nov;14(11):1041-1056. doi: 10.1080/15592294.2019.1633868. Epub 2019 Jul 11.

Abstract

Recent data from the Kollins lab ('Cannabinoid exposure and altered DNA methylation in rat and human sperm' Epigenetics 2018; 13: 1208-1221) indicated epigenetic effects of cannabis use on sperm in man parallel those in rats and showed substantial shifts in both hypo- and hyper-DNA methylation with the latter predominating. This provides one likely mechanism for the transgenerational transmission of epigenomic instability with sperm as the vector. It therefore contributes important pathophysiological insights into the probable mechanisms underlying the epidemiology of prenatal cannabis exposure potentially explaining diverse features of cannabis-related teratology including effects on the neuraxis, cardiovasculature, immune stimulation, secondary genomic instability and carcinogenesis related to both adult and pediatric cancers. The potentially inheritable and therefore multigenerational nature of these defects needs to be carefully considered in the light of recent teratological and neurobehavioural trends in diverse jurisdictions such as the USA nationally, Hawaii, Colorado, Canada, France and Australia, particularly relating to mental retardation, age-related morbidity and oncogenesis including inheritable cancerogenesis. Increasing demonstrations that the epigenome can respond directly and in real time and retain memories of environmental exposures of many kinds implies that the genome-epigenome is much more sensitive to environmental toxicants than has been generally realized. Issues of long-term multigenerational inheritance amplify these concerns. Further research particularly on the epigenomic toxicology of many cannabinoids is also required.

摘要

科林斯实验室的最新数据表明,大麻使用对人类精子的表观遗传影响与大鼠相似,并且在低甲基化和高甲基化中都存在大量的变化,后者占主导地位。这为精子作为载体传递表观基因组不稳定性的跨代传递提供了一种可能的机制。因此,它为理解产前大麻暴露的流行病学可能存在的机制提供了重要的病理生理学见解,这些机制可能解释了与大麻相关的畸形的不同特征,包括对神经轴、心血管系统、免疫刺激、二级基因组不稳定性和与成人和儿科癌症相关的致癌作用。鉴于美国全国、夏威夷、科罗拉多、加拿大、法国和澳大利亚等不同司法管辖区的最近的致畸和神经行为趋势,这些缺陷的潜在遗传性和因此的多代性质需要仔细考虑,特别是与智力迟钝、与年龄相关的发病率和肿瘤发生有关,包括遗传性癌症发生。越来越多的证据表明,表观基因组可以直接和实时做出反应,并保留对各种环境暴露的记忆,这意味着基因组-表观基因组对环境毒物的敏感性比人们通常认识到的要高得多。长期多代遗传的问题加剧了这些担忧。还需要进一步研究许多大麻素的表观基因组毒理学。

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