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TCDD-induced multi- and transgenerational changes in the methylome of male zebrafish gonads. TCDD诱导的雄性斑马鱼性腺甲基组的多代和跨代变化
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-09-27 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa010
Camille Akemann, Danielle N Meyer, Katherine Gurdziel, Tracie R Baker

The legacy endocrine disrupting chemical and aryl hydrocarbon receptor agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is produced as a byproduct of industrial processes and causes adverse health effects ranging from skin irritation to cancer. TCDD endpoints are also observed in subsequent, unexposed generations; however, the mechanisms of these multi- and transgenerational effects are unknown. We hypothesized an epigenetic mechanism, specifically DNA methylation for the transgenerational, male-mediated reproductive effects of developmental TCDD exposure. Using whole genome bisulfite sequencing, we evaluated DNA methylation changes in three generations of zebrafish, the first of which was exposed to TCDD during sexual development at 50 ppt for 1 h at both 3- and 7-week post-fertilization. We discovered that TCDD induces multi- and transgenerational methylomic changes in testicular tissue from zebrafish with decreased reproductive capacity, but most significantly in the indirectly exposed F1 generation. In comparing differentially methylated genes to concurrent transcriptomic changes, we identified several genes and pathways through which transgenerational effects of low level TCDD exposure are likely inherited. These include significant differential methylation of genes involved in reproduction, endocrine function, xenobiotic metabolism, and epigenetic processing. Notably, a number of histone modification genes were both differentially methylated and expressed in all generations, and many differentially methylated genes overlapped between multiple generations. Collectively, our results suggest that DNA methylation is a promising mechanism to explain male-mediated transgenerational reproductive effects of TCDD exposure in zebrafish, and these effects are likely inherited through integration of multiple epigenetic pathways.

2,3,7,8- 四氯二苯并对二恶英(TCDD)是一种传统的干扰内分泌的化学品和芳基烃受体激动剂,是工业生产过程中产生的副产品,会对健康造成从皮肤刺激到癌症等各种不利影响。在未接触过 TCDD 的后代中也能观察到 TCDD 的终点;然而,这些多代和跨代影响的机制尚不清楚。我们假设发育期暴露于 TCDD 会产生一种表观遗传机制,特别是 DNA 甲基化对男性生殖系统的跨代影响。利用全基因组亚硫酸氢盐测序,我们评估了三代斑马鱼的 DNA 甲基化变化,其中第一代斑马鱼在受精后 3 周和 7 周的有性发育过程中暴露于浓度为 50 ppt 的 TCDD 1 小时。我们发现,TCDD 会诱导斑马鱼睾丸组织发生多代和跨代的甲基组变化,生殖能力下降,但在间接暴露的 F1 代中变化最为显著。通过比较不同的甲基化基因和同时发生的转录组变化,我们确定了几个基因和途径,低水平 TCDD 暴露的跨代效应可能是通过这些基因和途径遗传的。其中包括与生殖、内分泌功能、异种生物代谢和表观遗传处理有关的基因的明显甲基化差异。值得注意的是,一些组蛋白修饰基因在所有世代中都有不同程度的甲基化和表达,许多不同程度的甲基化基因在多代之间重叠。总之,我们的研究结果表明,DNA甲基化是解释斑马鱼暴露于 TCDD 后雄性介导的跨代生殖效应的一种有希望的机制,而这些效应很可能是通过整合多种表观遗传途径而遗传的。
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引用次数: 0
Gestational exposure to particulate air pollution exacerbates the growth phenotypes induced by preconception paternal alcohol use: a multiplex model of exposure. 妊娠期暴露于颗粒空气污染加剧了由孕前父亲饮酒引起的生长表型:多重暴露模型。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-09-27 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa011
Toriq A Mustapha, Richard C Chang, Dennis Garcia-Rhodes, Drew Pendleton, Natalie M Johnson, Michael C Golding

It is now clear that parental histories of drug use, toxicant exposure, and social stress all have a significant influence on the health and development of the next generation. However, the ability of epigenetic parental life memories to interact with subsequent gestational exposures and cumulatively modify the developmental trajectory of the offspring remains an unexplored perspective in toxicology. Studies from our laboratory have identified male-specific postnatal growth restriction in a mouse model of chronic, preconception paternal alcohol exposure. The goal of the current study was to determine if paternal alcohol use, before conception, could modify the susceptibility of the offspring to a completely separate exposure encountered by the mother during pregnancy. In independent experiments, we previously identified altered developmental programming and increased markers of severe asthma induced by gestational exposure to particulate air pollution. In this study, male mice were exposed to either the control or alcohol preconception treatments, then mated to naive females, which we subsequently exposed to an ultrafine mixture of particulate matter via inhalation. Individually, neither preconception paternal drinking nor gestational exposures to particulate air pollution impacted the postnatal growth of female offspring. However, when both exposures were combined, females displayed a 30% reduction in weight gain. Unexpectedly, this exposure paradigm resulted in a dramatic postnatal increase in litter loss due to maternal cannibalism, which prevented additional measures of offspring health. These preliminary studies provide evidence of a complex interplay between preconception life history and intrauterine environmental factors in the control of postnatal growth.

现在很清楚,父母的药物使用史、毒物暴露史和社会压力都对下一代的健康和发育有重大影响。然而,表观遗传父母生活记忆与随后的妊娠暴露相互作用并累积改变后代发育轨迹的能力在毒理学中仍然是一个未探索的观点。我们实验室的研究在一个慢性、孕前父亲酒精暴露的小鼠模型中发现了雄性特异性的产后生长限制。当前研究的目的是确定父亲在怀孕前饮酒是否会改变后代对母亲在怀孕期间完全单独接触酒精的易感性。在之前的独立实验中,我们发现了妊娠期暴露于空气微粒污染中导致的发育程序改变和严重哮喘标志物增加。在这项研究中,雄性小鼠暴露于对照或酒精孕前处理,然后与幼稚的雌性交配,随后我们通过吸入将其暴露于超细颗粒物混合物中。就个体而言,孕前父亲饮酒和妊娠期暴露于颗粒空气污染中都不会影响女性后代的产后生长。然而,当这两种暴露结合在一起时,女性的体重增加减少了30%。出乎意料的是,这种暴露模式导致由于母亲同类相食而导致产仔损失的急剧增加,这阻碍了对后代健康的额外措施。这些初步研究提供了孕前生活史和宫内环境因素之间复杂的相互作用的证据,以控制出生后的生长。
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引用次数: 3
General anesthesia, germ cells and the missing heritability of autism: an urgent need for research. 全身麻醉、生殖细胞和自闭症遗传性的缺失:研究的迫切需要。
IF 4.8 Q1 GENETICS & HEREDITY Pub Date : 2020-07-18 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa007
Jill Escher, La Donna Ford

Agents of general anesthesia (GA) are commonly employed in surgical, dental and diagnostic procedures to effectuate global suppression of the nervous system, but in addition to somatic targets, the subject's germ cells-from the embryonic primordial stage to the mature gametes-may likewise be exposed. Although GA is generally considered safe for most patients, evidence has accumulated that various compounds, in particular the synthetic volatile anesthetic gases (SVAGs) such as sevoflurane, can exert neurotoxic, genotoxic and epigenotoxic effects, with adverse consequences for cellular and genomic function in both somatic and germline cells. The purpose of this paper is to review the evidence demonstrating that GA, and in particular, SVAGs, may in some circumstances adversely impact the molecular program of germ cells, resulting in brain and behavioral pathology in the progeny born of the exposed cells. Further, we exhort the medical and scientific communities to undertake comprehensive experimental and epidemiological research programs to address this critical gap in risk assessment.

全身麻醉(GA)制剂通常用于外科、牙科和诊断程序中,以实现对神经系统的全面抑制,但除了躯体目标外,受试者的生殖细胞--从胚胎原始阶段到成熟配子--也可能受到影响。虽然一般认为 GA 对大多数患者是安全的,但有证据表明,各种化合物,尤其是合成挥发性麻醉气体(SVAGs),如七氟醚,可能会产生神经毒性、基因毒性和表观遗传毒性效应,对体细胞和生殖细胞的细胞和基因组功能产生不利影响。本文旨在回顾证明 GA(尤其是 SVAGs)在某些情况下可能会对生殖细胞的分子程序产生不利影响的证据,从而导致暴露细胞的后代出现大脑和行为病理学。此外,我们呼吁医学界和科学界开展全面的实验和流行病学研究计划,以弥补风险评估中的这一重大缺陷。
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引用次数: 0
Transgenerational epigenetic reprogramming of early embryos: a mechanistic model. 早期胚胎的跨代表观遗传重编程:一个机制模型。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-07-18 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa009
Corrado Spadafora

The notion that epigenetic information can be transmitted across generations is supported by mounting waves of data, but the underlying mechanisms remain elusive. Here, a model is proposed which combines different lines of experimental evidence. First, it has been shown that somatic tissues exposed to stressing stimuli release circulating RNA-containing extracellular vesicles; second, epididymal spermatozoa can take up, internalize and deliver the RNA-containing extracellular vesicles to oocytes at fertilization; third, early embryos can process RNA-based information. These elements constitute the building blocks upon which the model is built. The model proposes that a continuous stream of epigenetic information flows from parental somatic tissues to the developing embryos. The flow can cross the Weismann barrier, is mediated by circulating vesicles and epididymal spermatozoa, and has the potential to generate epigenetic traits that are then stably acquired in the offspring. In a broader perspective, it emerges that a natural 'assembly line' operates continuously, aiming at passing the parental epigenetic blueprint in growing embryos.

表观遗传信息可以跨代传递的观点得到了大量数据的支持,但其潜在机制仍然难以捉摸。在这里,我们提出了一个结合不同实验证据线的模型。首先,研究表明,暴露于应激刺激的体细胞组织释放含有循环rna的细胞外囊泡;其次,附睾精子可以在受精时摄取、内化含rna的细胞外囊泡并将其传递给卵母细胞;第三,早期胚胎可以处理基于rna的信息。这些元素构成了构建模型的构建块。该模型提出,一个连续的表观遗传信息流从亲代体细胞组织流向发育中的胚胎。这种流动可以穿过魏斯曼屏障,由循环囊泡和附睾精子介导,并有可能产生表观遗传性状,然后在后代中稳定地获得。从更广泛的角度来看,一条自然的“装配线”不断地运行,旨在将亲本的表观遗传蓝图传递给生长中的胚胎。
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引用次数: 11
DNA methylation reprogramming in medaka fish, a promising animal model for environmental epigenetics research. 环境表观遗传学研究中有前景的动物模型——medaka鱼的DNA甲基化重编程。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-07-07 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa008
Xuegeng Wang, Ramji K Bhandari

DNA methylation is a major epigenetic modification that undergoes dramatic changes in two epigenetic reprogramming windows during development: first in preimplantation embryos and second in primordial germ cell (PGC) specification. In both windows, DNA methylation patterns are reprogrammed genome-wide, and the majority of inherited methylation marks are erased, generating cells with broad developmental potential. Recent studies reported that the reprogramming of genome methylation in medaka is similar to human and mouse, suggesting that medaka may serve as a suitable biomedical model for comparative studies focused on the epigenetic and transgenerational inheritance of phenotypic traits. In this mini review, we will discuss how somatic and germ cells in post-fertilization stage embryos are epigenetically reprogrammed in mammals and fishes with a particular focus on DNA methylation dynamics.

DNA甲基化是一种主要的表观遗传修饰,在胚胎发育过程中的两个表观遗传重编程窗口中经历了巨大的变化:第一个在着床前胚胎中,第二个在原始生殖细胞(PGC)规范中。在这两个窗口中,DNA甲基化模式在全基因组范围内被重新编程,大多数遗传甲基化标记被删除,产生具有广泛发育潜力的细胞。最近的研究报道,medaka基因组甲基化的重编程与人类和小鼠相似,这表明medaka可以作为一种合适的生物医学模型,用于表型性状的表观遗传和跨代遗传的比较研究。在这篇综述中,我们将讨论哺乳动物和鱼类受精后胚胎的体细胞和生殖细胞是如何进行表观遗传重编程的,并特别关注DNA甲基化动力学。
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引用次数: 16
Epigenetic biomarkers and preterm birth. 表观遗传生物标志物与早产。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-06-14 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa005
Bongsoo Park, Rasheda Khanam, Vinesh Vinayachandran, Abdullah H Baqui, Stephanie J London, Shyam Biswal

Preterm birth (PTB) is a major public health challenge, and novel, sensitive approaches to predict PTB are still evolving. Epigenomic markers are being explored as biomarkers of PTB because of their molecular stability compared to gene expression. This approach is also relatively new compared to gene-based diagnostics, which relies on mutations or single nucleotide polymorphisms. The fundamental principle of epigenome diagnostics is that epigenetic reprogramming in the target tissue (e.g. placental tissue) might be captured by more accessible surrogate tissue (e.g. blood) using biochemical epigenome assays on circulating DNA that incorporate methylation, histone modifications, nucleosome positioning, and/or chromatin accessibility. Epigenomic-based biomarkers may hold great potential for early identification of the majority of PTBs that are not associated with genetic variants or mutations. In this review, we discuss recent advances made in the development of epigenome assays focusing on its potential exploration for association and prediction of PTB. We also summarize population-level cohort studies conducted in the USA and globally that provide opportunities for genetic and epigenetic marker development for PTB. In addition, we summarize publicly available epigenome resources and published PTB studies. We particularly focus on ongoing genome-wide DNA methylation and epigenome-wide association studies. Finally, we review the limitations of current research, the importance of establishing a comprehensive biobank, and possible directions for future studies in identifying effective epigenome biomarkers to enhance health outcomes for pregnant women at risk of PTB and their infants.

早产(PTB)是一项重大的公共卫生挑战,预测PTB的新颖、敏感的方法仍在不断发展。由于表观基因组标记与基因表达相比具有分子稳定性,因此正被探索作为PTB的生物标记物。与依赖突变或单核苷酸多态性的基于基因的诊断相比,这种方法也相对较新。表观基因组诊断的基本原理是,目标组织(如胎盘组织)中的表观遗传重编程可能被更容易获得的替代组织(如血液)捕获,使用生化表观基因组分析循环DNA,包括甲基化,组蛋白修饰,核小体定位和/或染色质可及性。基于表观基因组学的生物标志物可能对大多数与遗传变异或突变无关的ptb的早期识别具有很大的潜力。在这篇综述中,我们讨论了近年来在表观基因组分析的发展进展,重点是其潜在的探索与肺结核的关联和预测。我们还总结了在美国和全球进行的人群水平队列研究,这些研究为PTB的遗传和表观遗传标记的开发提供了机会。此外,我们总结了公开可用的表观基因组资源和已发表的PTB研究。我们特别关注正在进行的全基因组DNA甲基化和表观全基因组关联研究。最后,我们回顾了目前研究的局限性,建立一个全面的生物库的重要性,以及未来研究的可能方向,以确定有效的表观基因组生物标志物,以提高妊娠妇女和她们的婴儿的健康结局。
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引用次数: 14
Placental lncRNA expression associated with placental cadmium concentrations and birth weight. 胎盘 lncRNA 表达与胎盘镉浓度和出生体重相关。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-05-10 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa003
Michael R Hussey, Amber Burt, Maya A Deyssenroth, Brian P Jackson, Ke Hao, Shouneng Peng, Jia Chen, Carmen J Marsit, Todd M Everson

Heavy metal exposures, such as cadmium, can have negative effects on infant birth weight (BW)-among other developmental outcomes-with placental dysfunction potentially playing a role in these effects. In this study, we examined how differential placental expression of long non-coding RNAs (lncRNAs) may be associated with cadmium levels in placenta and whether differences in the expression of those lncRNAs were associated with fetal growth. In the Rhode Island Child Health Study, we used data from Illumina HiSeq whole transcriptome RNA sequencing (n = 199) to examine association between lncRNA expression and measures of infant BW as well as placental cadmium concentrations controlled for appropriate covariates. Of the 1191 lncRNAs sequenced, 46 demonstrated associations (q < 0.05) with BW in models controlling for infant sex, maternal age, BMI, maternal education, and smoking during pregnancy. Furthermore, four of these transcripts were associated with placental cadmium concentrations, with MIR22HG and ERVH48-1 demonstrating increases in expression associated with increasing cadmium exposure and elevated odds of small for gestational age birth, while AC114763.2 and LINC02595 demonstrated reduced expression associated with cadmium, but elevated odds of large for gestational age birth with increasing expression. We identified relationships between lncRNA expression with both placental cadmium concentrations and BW. This study provides evidence that disrupted placental expression of lncRNAs may be a part of cadmium's mechanisms of reproductive toxicity.

重金属(如镉)暴露会对婴儿出生体重(BW)及其他发育结果产生负面影响,而胎盘功能障碍可能在这些影响中起到一定作用。在这项研究中,我们研究了胎盘中长非编码 RNA(lncRNA)的不同表达可能与胎盘中的镉水平有何关联,以及这些 lncRNA 的表达差异是否与胎儿的生长有关。在罗德岛儿童健康研究(Rhode Island Child Health Study)中,我们利用Illumina HiSeq全转录组RNA测序数据(n = 199)研究了lncRNA表达与婴儿体重测量以及胎盘镉浓度之间的关系,并控制了适当的协变量。在测序的1191个lncRNA中,46个表现出相关性(q MIR22HG和ERVH48-1表现出与镉暴露增加相关的表达增加以及小胎龄出生几率升高,而AC114763.2和LINC02595表现出与镉相关的表达降低,但随着表达增加,大胎龄出生几率升高。我们确定了 lncRNA 表达与胎盘镉浓度和体重之间的关系。这项研究提供的证据表明,lncRNA的胎盘表达紊乱可能是镉的生殖毒性机制的一部分。
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引用次数: 0
Symposium summary: Epigenetic inheritance-impact for biology and society 26-28 August 2019, Zurich, Switzerland. 2019年8月26-28日,瑞士苏黎世,表观遗传对生物学和社会的影响
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-05-06 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa004
Irina Lazar-Contes, Martin Roszkowski, Deepak K Tanwar, Isabelle M Mansuy

The concept of epigenetic inheritance proposes a new and unconventional way to think about heredity in health and disease, at the interface between genetics and the environment. Epigenetic inheritance is a form of biological inheritance not encoded in the DNA sequence itself but mediated by epigenetic factors. Because epigenetic factors can be modulated by the environment, they can relay this information to the genome and modify its activity consequentially. If epigenetic changes induced by environmental exposure are present in the germline and persist in germ cells during development until conception, they have the potential to transfer the traces of ancestral exposure to the progeny. This form of heredity relates to the extremely important question of nature versus nurture and how much of our own make-up is genetically or epigenetically determined, a question that remains largely unresolved. Because it questions the dominant dogma of genetics and brings a paradigm shift in sciences, it has to creating strong bridges between disciplines and provide solid causal evidence to be firmly established. The second edition of a conference fully dedicated to epigenetic inheritance was held in August 2019 in Zurich, Switzerland. This symposium titled 'Epigenetic inheritance: impact for biology and society' (http://www.epigenetic-inheritance-zurich.ethz.ch), gathered experts in the field of epigenetic inheritance to discuss the concept and pertinent findings, exchange views and expertise about models and methods, and address challenges raised by this new discipline. The symposium offered a mix of invited lectures and short talks selected from abstracts, poster sessions and a workshop 'Meet the experts: Q&A'. A tour of a local omics facility the Functional Genomics Center Zurich was also offered to interested participants. Additional comments and impressions were shared by attendees on Twitter #eisz19 during and after the symposium. This summary provides an overview of the different sessions and talks and describes the main findings presented.

表观遗传的概念提出了一种新的和非传统的方式来思考健康和疾病中的遗传,在遗传学和环境之间的接口。表观遗传是一种不以DNA序列本身编码,而是由表观遗传因子介导的生物遗传形式。由于表观遗传因素可以被环境调节,它们可以将这些信息传递给基因组并相应地改变其活性。如果由环境暴露引起的表观遗传变化存在于生殖细胞中,并在发育过程中持续存在于生殖细胞中直至受孕,则它们有可能将祖先暴露的痕迹转移给后代。这种形式的遗传关系到一个极其重要的问题,即先天与后天,以及我们自身的构成有多少是由遗传或表观遗传决定的,这个问题在很大程度上仍未得到解决。因为它质疑了遗传学的主导教条,并带来了科学范式的转变,它必须在学科之间建立牢固的桥梁,并提供坚实的因果证据,才能牢固地建立起来。2019年8月,第二届专门讨论表观遗传的会议在瑞士苏黎世举行。本次研讨会题为“表观遗传:对生物学和社会的影响”(http://www.epigenetic-inheritance-zurich.ethz.ch),聚集了表观遗传领域的专家,讨论了表观遗传的概念和相关发现,交流了关于模型和方法的观点和专业知识,并解决了这一新学科提出的挑战。研讨会提供了邀请讲座和从摘要中挑选的简短演讲,海报会议和“与专家会面:问答”研讨会。有兴趣的参与者还可以参观苏黎世功能基因组学中心的当地组学设施。在研讨会期间和之后,与会者在Twitter #eisz19上分享了其他评论和印象。本摘要提供了不同会议和演讲的概述,并描述了提出的主要发现。
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引用次数: 2
Erratum: Acetaminophen use during pregnancy and DNA methylation in the placenta of the extremely low gestational age newborn (ELGAN) cohort. 更正:怀孕期间对乙酰氨基酚的使用和极低胎龄新生儿(ELGAN)队列胎盘中的DNA甲基化。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-05-06 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa006
Kezia A Addo, Catherine Bulka, Radhika Dhingra, Hudson P Santos, Lisa Smeester, T Michael O'Shea, Rebecca C Fry

[This corrects the article DOI: 10.1093/eep/dvz010.][This corrects the article DOI: 10.1093/eep/dvz010.].

[这更正了文章DOI: 10.1093/eep/dvz010。][更正文章DOI: 10.1093/eep/dvz010.]。
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引用次数: 30
Cannabis use and the sperm epigenome: a budding concern? 大麻使用和精子表观基因组:一个崭露头角的问题?
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2020-03-19 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa002
Rose Schrott, Susan K Murphy

The United States is swiftly moving toward increased legalization of medical and recreational cannabis. Currently considered the most commonly used illicit psychoactive drug, recreational cannabis is legal in 11 states and Washington, DC, and male use is an important and understudied concern. Questions remain, however, about the potential long-term consequences of this exposure and how cannabis might impact the epigenetic integrity of sperm in such a way that could influence the health and development of offspring. This review summarizes cannabis use and potency in the USA, provides a brief overview of DNA methylation as an epigenetic mechanism that is vulnerable in sperm to environmental exposures including cannabis, and summarizes studies that have examined the effects of parental exposure to cannabis or delta-9 tetrahydrocannabinol (THC, the main psychoactive component of cannabis) on the epigenetic profile of the gametes and behavior of offspring. These studies have demonstrated significant changes to the sperm DNA methylome following cannabis use in humans, and THC exposure in rats. Furthermore, the use of rodent models has shown methylation and behavioral changes in rats born to fathers exposed to THC or synthetic cannabinoids, or to parents who were both exposed to THC. These data substantiate an urgent need for additional studies assessing the effects of cannabis exposure on childhood health and development. This is especially true given the current growing state of cannabis use in the USA.

美国正在迅速走向医用和娱乐用大麻的合法化。娱乐性大麻目前被认为是最常用的非法精神药物,在11个州和华盛顿特区是合法的,男性使用大麻是一个重要的问题,但尚未得到充分研究。然而,关于这种接触的潜在长期后果,以及大麻如何影响精子的表观遗传完整性,从而影响后代的健康和发育,问题仍然存在。这篇综述总结了大麻在美国的使用和效力,简要概述了DNA甲基化作为精子易受包括大麻在内的环境暴露的表观遗传机制,并总结了父母暴露于大麻或德尔塔-9四氢大麻酚(THC,大麻的主要精神活性成分)对后代配子表观遗传谱和行为的影响的研究。这些研究表明,在人类使用大麻和大鼠接触四氢大麻酚后,精子DNA甲基组发生了重大变化。此外,啮齿类动物模型的使用表明,暴露于四氢大麻酚或合成大麻素的父亲或暴露于四氢大麻酚的父母所生的大鼠的甲基化和行为变化。这些数据证实,迫切需要进行更多的研究,评估接触大麻对儿童健康和发育的影响。考虑到目前美国大麻使用的增长状态,这一点尤其正确。
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引用次数: 19
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Environmental Epigenetics
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