Pub Date : 2022-04-16eCollection Date: 2022-01-01DOI: 10.1093/eep/dvac011
Miriam Kretschmer, Katharina Gapp
The inheritance of neurophysiologic and neuropsychologic complex diseases can only partly be explained by the Mendelian concept of genetic inheritance. Previous research showed that both psychological disorders like post-traumatic stress disorder and metabolic diseases are more prevalent in the progeny of affected parents. This could suggest an epigenetic mode of transmission. Human studies give first insight into the scope of intergenerational influence of stressors but are limited in exploring the underlying mechanisms. Animal models have elucidated the mechanistic underpinnings of epigenetic transmission. In this review, we summarize progress on the mechanisms of paternal intergenerational transmission by means of sperm RNA in mouse models. We discuss relevant details for the modelling of RNA-mediated transmission, point towards currently unanswered questions and propose experimental considerations for tackling these questions.
{"title":"Deciphering the RNA universe in sperm in its role as a vertical information carrier.","authors":"Miriam Kretschmer, Katharina Gapp","doi":"10.1093/eep/dvac011","DOIUrl":"10.1093/eep/dvac011","url":null,"abstract":"<p><p>The inheritance of neurophysiologic and neuropsychologic complex diseases can only partly be explained by the Mendelian concept of genetic inheritance. Previous research showed that both psychological disorders like post-traumatic stress disorder and metabolic diseases are more prevalent in the progeny of affected parents. This could suggest an epigenetic mode of transmission. Human studies give first insight into the scope of intergenerational influence of stressors but are limited in exploring the underlying mechanisms. Animal models have elucidated the mechanistic underpinnings of epigenetic transmission. In this review, we summarize progress on the mechanisms of paternal intergenerational transmission by means of sperm RNA in mouse models. We discuss relevant details for the modelling of RNA-mediated transmission, point towards currently unanswered questions and propose experimental considerations for tackling these questions.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2022-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48717375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marion Julia Lamb, a pioneer in the field of evolutionary epigenetics, died in London on the 12th of December 2021 at the age of 82 of lung cancer. Marion was an original and accomplished scientist and her intellectual brilliance was combined with deep political and intellectual courage, a fascination with the natural world and an almost fanatical studiousness. Coming from a natureand bookloving working-class family, she roamed, as a child, the coasts and estuaries of East Anglia, watching birds, investigating rock pools, turning every rotten log, developing the naturalist’s ardent and focused competence. She was always grateful to her parents for the freedom they gave her and for their one demand—that she ‘does her best’—whatever ‘best’ may be. And indeed she did—from decorating her flat to gardening, sailing, teaching and researching. Her intellect was clear and powerful and she excelled in everything she ever put it to—as a 16-year-old lab assistant in Max Perutz’s lab in Cambridge during her high-school vacations, as a brilliant university student (she shared with Robin Weiss the Francis Perch Bedford Prize for the best first degree in University College London), as an inspiring teacher and as a ground-breaking scientist. Marion loved the elegant beauty of genetics, and when John Maynard Smith, her genetics teacher in University College London (UCL) suggested that she does a PhD with him, she was delighted. Her thesis on ‘Radiation and Ageing in Drosophila’ was awarded a PhD in 1965. Her laboratory research was conducted in UCL, Harwell and Birkbeck College (where she became a senior lecturer) and was concerned mainly with various aspects of the biology and genetics of ageing, using Drosophila as a research tool. Her large body of experimental work on ageing, radiation biology and mutagenesis, 25 papers altogether, stood the test of time, and she wrote a highly acclaimed, crystal-clear and concise book ‘The Biology of Ageing’ (published by Blackie, 1), on which several advanced courses in the biology of ageing around the world were based. Evolutionary biology was Marion’s passion and guide since she was a high-school student and read Huxley’s Evolution: The Modern Synthesis. She told me that the first tutorial she ever attended as a first-year student in UCL was on Waddington’s The Strategy of the Genes and that it blew her mind. Our first conversation, in 1973, also happened to be about Waddington (I discovered Waddington, independently, through reading Arthur Koestler’s Ghost in the Machine, well before I knew any genetics). I was a first-year student, and she was my genetics teacher in Birkbeck College, where I spent a year. I asked her if she knowsWaddington and she looked at me with a wry smile and suggested that I learn to walk before I start running. I ended up doing a PhD in genetics. Long before we started writing papers together, Marion sent me evolutionary biology books to Israel, and when we met we discussed the many hot topics of
进化表观遗传学领域的先驱Marion Julia Lamb于2021年12月12日在伦敦因肺癌癌症去世,享年82岁。马里恩是一位富有独创性和成就的科学家,她的智慧才华与深厚的政治和智力勇气、对自然世界的迷恋以及近乎狂热的勤奋相结合。她来自一个自然、爱读书的工人阶级家庭,小时候在东安格利亚的海岸和河口漫步,观察鸟类,调查岩石池,翻遍每一根腐烂的原木,培养这位博物学家热情而专注的能力。她一直感谢父母给她的自由,感谢他们的一个要求——她“尽自己最大的努力”——无论“最好的”是什么。事实上,她做到了——从装饰公寓到园艺、航海、教学和研究。她的智慧清晰而强大,她在所有方面都表现出色——高中假期时,她是剑桥Max Perutz实验室的一名16岁实验室助理,还是一名才华横溢的大学生(她与Robin Weiss共同获得了伦敦大学学院最佳第一学位Francis Perch Bedford奖),作为一位鼓舞人心的老师和一位开拓性的科学家。Marion喜欢遗传学的优雅之美,当她在伦敦大学学院(UCL)的遗传学老师John Maynard Smith建议她和他一起攻读博士学位时,她很高兴。她的论文“果蝇的辐射与衰老”于1965年获得博士学位。她的实验室研究在伦敦大学学院、哈维尔和伯克贝克学院进行(在那里她成为了一名高级讲师),主要研究衰老的生物学和遗传学的各个方面,将果蝇作为研究工具。她在衰老、辐射生物学和诱变方面的大量实验工作,总共25篇论文,经受住了时间的考验,她写了一本广受好评、清晰简洁的书《衰老生物学》(由Blackie出版,1),这本书是世界各地衰老生物学的几门高级课程的基础。从Marion还是一名高中生的时候起,进化生物学就是她的热情和指南,她阅读了Huxley的《进化:现代合成》。她告诉我,她在伦敦大学学院一年级时参加的第一个教程是沃丁顿的《基因策略》,这让她大吃一惊。1973年,我们的第一次对话碰巧也是关于沃丁顿的(早在我了解任何遗传学之前,我就通过阅读亚瑟·科斯勒的《机器中的幽灵》独立发现了沃丁顿)。我是一年级的学生,她是我在伯克贝克学院的遗传学老师,我在那里度过了一年。我问她是否知道沃丁顿,她苦笑着看着我,建议我在开始跑步之前先学会走路。我最终获得了遗传学博士学位。早在我们开始一起写论文之前,马里恩就给我寄了进化生物学的书到以色列,当我们见面时,我们讨论了当时的许多热门话题——间断平衡、社会生物学辩论、自私基因和中立者选择辩论。几年后,也就是20世纪80年代初,我们开始合作,探索表观遗传的进化含义。这不是一个主流话题(委婉地说),我们对它的兴趣与我们的背景有关——马里恩在英国进化生物学学院接受教育,在20世纪50年代和60年代初,该学院比美国同行更容易接受非正统遗传和进化模式的可能性,我之所以来到生物学,是因为我对哲学感兴趣,以及围绕进化论的激烈争论。我们更直接的动机与我们当时在遗传学和染色质生物学方面的实验工作有关。1982年末,我开始在希伯来大学遗传学系攻读博士学位,研究DNA甲基化与染色体复制时间之间的关系。我使用了两条X染色体可以在形态学上区分的雌性细胞系,并询问当用去甲基剂5-氮杂胞苷处理细胞时,失活的X染色体是否可以改变其失活的浓缩染色质构象及其复制晚期。答案是肯定的,但我发现的全染色体效应是短暂的。这表明DNA甲基化和染色质变化的动力学比迄今为止认为的更灵活。Marion当时正在研究衰老对果蝇多线染色体的影响,发现染色质结构随着年龄的增长而变化(不幸的是,她从未发表过这些结果)。我们认为,一方面,染色质状态在细胞谱系中的稳定传播性,另一方面,这些状态的发育反应性,揭示了非常有趣的进化问题和可能性。 我们认为,在配子发生过程中,过去诱导的染色质变异的所有痕迹都会被删除,这是不可信的。只要保持全能性,染色质变异,就像遗传变异一样,可以通过种系遗传。我们推断,由于染色质状态可以在环境中诱导,在发育过程中获得的染色质变异可能会在几代人之间传递。由于我们的框架是进化的,我们决定研究X染色体在发育和进化过程中的激活和失活动力学。我们关注减数分裂配对对染色质组织的发育影响,并询问染色体发育动力学如何影响性染色体的进化。这些调查产生了两篇论文。我们的第一篇联合发表的论文是“减数分裂配对约束和性染色体的活性”[2](1986年完成,但经过多次反复后于1988年发表),第二篇
{"title":"Marion Julia Lamb (29 July 1939–12 December 2021)","authors":"E. Jablonka","doi":"10.1093/eep/dvac009","DOIUrl":"https://doi.org/10.1093/eep/dvac009","url":null,"abstract":"Marion Julia Lamb, a pioneer in the field of evolutionary epigenetics, died in London on the 12th of December 2021 at the age of 82 of lung cancer. Marion was an original and accomplished scientist and her intellectual brilliance was combined with deep political and intellectual courage, a fascination with the natural world and an almost fanatical studiousness. Coming from a natureand bookloving working-class family, she roamed, as a child, the coasts and estuaries of East Anglia, watching birds, investigating rock pools, turning every rotten log, developing the naturalist’s ardent and focused competence. She was always grateful to her parents for the freedom they gave her and for their one demand—that she ‘does her best’—whatever ‘best’ may be. And indeed she did—from decorating her flat to gardening, sailing, teaching and researching. Her intellect was clear and powerful and she excelled in everything she ever put it to—as a 16-year-old lab assistant in Max Perutz’s lab in Cambridge during her high-school vacations, as a brilliant university student (she shared with Robin Weiss the Francis Perch Bedford Prize for the best first degree in University College London), as an inspiring teacher and as a ground-breaking scientist. Marion loved the elegant beauty of genetics, and when John Maynard Smith, her genetics teacher in University College London (UCL) suggested that she does a PhD with him, she was delighted. Her thesis on ‘Radiation and Ageing in Drosophila’ was awarded a PhD in 1965. Her laboratory research was conducted in UCL, Harwell and Birkbeck College (where she became a senior lecturer) and was concerned mainly with various aspects of the biology and genetics of ageing, using Drosophila as a research tool. Her large body of experimental work on ageing, radiation biology and mutagenesis, 25 papers altogether, stood the test of time, and she wrote a highly acclaimed, crystal-clear and concise book ‘The Biology of Ageing’ (published by Blackie, 1), on which several advanced courses in the biology of ageing around the world were based. Evolutionary biology was Marion’s passion and guide since she was a high-school student and read Huxley’s Evolution: The Modern Synthesis. She told me that the first tutorial she ever attended as a first-year student in UCL was on Waddington’s The Strategy of the Genes and that it blew her mind. Our first conversation, in 1973, also happened to be about Waddington (I discovered Waddington, independently, through reading Arthur Koestler’s Ghost in the Machine, well before I knew any genetics). I was a first-year student, and she was my genetics teacher in Birkbeck College, where I spent a year. I asked her if she knowsWaddington and she looked at me with a wry smile and suggested that I learn to walk before I start running. I ended up doing a PhD in genetics. Long before we started writing papers together, Marion sent me evolutionary biology books to Israel, and when we met we discussed the many hot topics of","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42918750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An Oxford University Press publication, ‘Environmental Epigenetics’, just initiated its eighth year of operations with this Volume 8 Issue 1. We are a 100% open access journal listed in PubMed Central, along with numerous other access sites. Environmental Epigenetics is in review to obtain an impact factor in 2022. Special issues have occurred each year, and we encourage requests for special issues in environmental epigenetics. Our Special Issues in 2021–22 were on Epigenetic Transgenerational Inheritance, Generational Toxicology, and Environmental Epigenetics and Evolution (https://academic.oup.com/eep/pages/special_issues). The amount and diversity of our published studies are increasing as the field of environmental epigenetics grows and expands. We are looking forward to another productive year and encourage you to consider submissions to ‘Environmental Epigenetics’.
{"title":"Environmental Epigenetics 2022 update","authors":"M. Skinner","doi":"10.1093/eep/dvac008","DOIUrl":"https://doi.org/10.1093/eep/dvac008","url":null,"abstract":"An Oxford University Press publication, ‘Environmental Epigenetics’, just initiated its eighth year of operations with this Volume 8 Issue 1. We are a 100% open access journal listed in PubMed Central, along with numerous other access sites. Environmental Epigenetics is in review to obtain an impact factor in 2022. Special issues have occurred each year, and we encourage requests for special issues in environmental epigenetics. Our Special Issues in 2021–22 were on Epigenetic Transgenerational Inheritance, Generational Toxicology, and Environmental Epigenetics and Evolution (https://academic.oup.com/eep/pages/special_issues). The amount and diversity of our published studies are increasing as the field of environmental epigenetics grows and expands. We are looking forward to another productive year and encourage you to consider submissions to ‘Environmental Epigenetics’.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44305879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-01eCollection Date: 2022-01-01DOI: 10.1093/eep/dvac006
Albert Stuart Reece, Gary Kenneth Hulse
Breast cancer (BC) is the commonest human cancer and its incidence (BC incidence, BCI) is rising worldwide. Whilst both tobacco and alcohol have been linked to BCI genotoxic cannabinoids have not been investigated. Age-adjusted state-based BCI 2003-2017 was taken from the Surveillance Epidemiology and End Results database of the Centers for Disease Control. Drug use from the National Survey of Drug Use and Health, response rate 74.1%. Median age, median household income and ethnicity were from US census. Inverse probability weighted (ipw) multivariable regression conducted in R. In bivariate analysis BCI was shown to be significantly linked with rising cannabis exposure {β-est. = 3.93 [95% confidence interval 2.99, 4.87], P = 1.10 × 10-15}. At 8 years lag cigarettes:cannabis [β-est. = 2660 (2150.4, 3169.3), P = 4.60 × 10-22] and cannabis:alcoholism [β-est. = 7010 (5461.6, 8558.4), P = 1.80 × 10-17] were significant in ipw-panel regression. Terms including cannabidiol [CBD; β-est. = 16.16 (0.39, 31.93), P = 0.446] and cannabigerol [CBG; β-est. = 6.23 (2.06, 10.39), P = 0.0034] were significant in spatiotemporal models lagged 1:2 years, respectively. Cannabis-liberal paradigms had higher BCI [67.50 ± 0.26 v. 65.19 ± 0.21/100 000 (mean ± SEM), P = 1.87 × 10-11; β-est. = 2.31 (1.65, 2.96), P = 9.09 × 10-12]. 55/58 expected values >1.25 and 13/58 >100. Abortion was independently and causally significant in space-time models. Data show that exposure to cannabis and the cannabinoids Δ9-tetrahydrocannabinol, CBD, CBG and alcoholism fulfil quantitative causal criteria for BCI across space and time. Findings are robust to adjustment for age and several known sociodemographic, socio-economic and hormonal risk factors and establish cannabinoids as an additional risk factor class for breast carcinogenesis. BCI is higher under cannabis-liberal legal paradigms.
{"title":"Geospatiotemporal and causal inference study of cannabis and other drugs as risk factors for female breast cancer USA 2003-2017.","authors":"Albert Stuart Reece, Gary Kenneth Hulse","doi":"10.1093/eep/dvac006","DOIUrl":"10.1093/eep/dvac006","url":null,"abstract":"<p><p>Breast cancer (BC) is the commonest human cancer and its incidence (BC incidence, BCI) is rising worldwide. Whilst both tobacco and alcohol have been linked to BCI genotoxic cannabinoids have not been investigated. Age-adjusted state-based BCI 2003-2017 was taken from the Surveillance Epidemiology and End Results database of the Centers for Disease Control. Drug use from the National Survey of Drug Use and Health, response rate 74.1%. Median age, median household income and ethnicity were from US census. Inverse probability weighted (ipw) multivariable regression conducted in R. In bivariate analysis BCI was shown to be significantly linked with rising cannabis exposure {β-est. = 3.93 [95% confidence interval 2.99, 4.87], <i>P</i> = 1.10 × 10<sup>-15</sup>}. At 8 years lag cigarettes:cannabis [β-est. = 2660 (2150.4, 3169.3), <i>P</i> = 4.60 × 10<sup>-22</sup>] and cannabis:alcoholism [β-est. = 7010 (5461.6, 8558.4), <i>P</i> = 1.80 × 10<sup>-17</sup>] were significant in ipw-panel regression. Terms including cannabidiol [CBD; β-est. = 16.16 (0.39, 31.93), <i>P</i> = 0.446] and cannabigerol [CBG; β-est. = 6.23 (2.06, 10.39), <i>P</i> = 0.0034] were significant in spatiotemporal models lagged 1:2 years, respectively. Cannabis-liberal paradigms had higher BCI [67.50 ± 0.26 v. 65.19 ± 0.21/100 000 (mean ± SEM), <i>P</i> = 1.87 × 10<sup>-11</sup>; β-est. = 2.31 (1.65, 2.96), <i>P</i> = 9.09 × 10<sup>-12</sup>]. 55/58 expected values >1.25 and 13/58 >100. Abortion was independently and causally significant in space-time models. Data show that exposure to cannabis and the cannabinoids Δ9-tetrahydrocannabinol, CBD, CBG and alcoholism fulfil quantitative causal criteria for BCI across space and time. Findings are robust to adjustment for age and several known sociodemographic, socio-economic and hormonal risk factors and establish cannabinoids as an additional risk factor class for breast carcinogenesis. BCI is higher under cannabis-liberal legal paradigms.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"60653128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-18eCollection Date: 2022-01-01DOI: 10.1093/eep/dvac005
Rashmi Joglekar, Carole Grenier, Cathrine Hoyo, Kate Hoffman, Susan K Murphy
Metastable epialleles (MEs) are genomic regions that are stochastically methylated prior to germ layer specification and exhibit high interindividual but low intra-individual variability across tissues. ME methylation is vulnerable to environmental stressors, including diet. Tobacco smoke (TS) exposure during pregnancy is associated with adverse impacts on fetal health and maternal micronutrient levels as well as altered methylation. Our objective was to determine if maternal smoke exposure impacts methylation at MEs. Consistent with prior studies, we observed reductions in one-carbon pathway micronutrients with gestational TS exposure, including maternal folate (P = 0.02) and vitamins B6 (P = 0.05) and B12 (P = 0.007). We examined putative MEs BOLA3, PAX8, and ZFYVE28 in cord blood specimens from 85 Newborn Epigenetics STudy participants. Gestational TS exposure was associated with elevated DNA methylation at PAX8 (+5.22% average methylation; 95% CI: 0.33% to 10.10%; P = 0.037). In human conceptal kidney tissues, higher PAX8 transcription was associated with lower methylation (Rs = 0.55; P = 0.07), suggesting that the methylation levels established at MEs, and their environmentally induced perturbation, may have meaningful, tissue-specific functional consequences. This may be particularly important because PAX8 is implicated in several cancers, including pediatric kidney cancer. Our data are the first to indicate vulnerability of human ME methylation establishment to TS exposure, with a general trend of increasing levels of methylation at these loci. Further investigation is needed to determine how TS exposure-mediated changes in DNA methylation at MEs, and consequent expression levels, might affect smoking-related disease risk.
{"title":"Maternal tobacco smoke exposure is associated with increased DNA methylation at human metastable epialleles in infant cord blood.","authors":"Rashmi Joglekar, Carole Grenier, Cathrine Hoyo, Kate Hoffman, Susan K Murphy","doi":"10.1093/eep/dvac005","DOIUrl":"10.1093/eep/dvac005","url":null,"abstract":"<p><p>Metastable epialleles (MEs) are genomic regions that are stochastically methylated prior to germ layer specification and exhibit high interindividual but low intra-individual variability across tissues. ME methylation is vulnerable to environmental stressors, including diet. Tobacco smoke (TS) exposure during pregnancy is associated with adverse impacts on fetal health and maternal micronutrient levels as well as altered methylation. Our objective was to determine if maternal smoke exposure impacts methylation at MEs. Consistent with prior studies, we observed reductions in one-carbon pathway micronutrients with gestational TS exposure, including maternal folate (<i>P</i> = 0.02) and vitamins B6 (<i>P</i> = 0.05) and B12 (<i>P</i> = 0.007). We examined putative MEs <i>BOLA3, PAX8,</i> and <i>ZFYVE28</i> in cord blood specimens from 85 Newborn Epigenetics STudy participants. Gestational TS exposure was associated with elevated DNA methylation at <i>PAX8</i> (+5.22% average methylation; 95% CI: 0.33% to 10.10%; <i>P</i> = 0.037). In human conceptal kidney tissues, higher <i>PAX8</i> transcription was associated with lower methylation (<i>R</i> <sub>s</sub> = 0.55; <i>P</i> = 0.07), suggesting that the methylation levels established at MEs, and their environmentally induced perturbation, may have meaningful, tissue-specific functional consequences. This may be particularly important because <i>PAX8</i> is implicated in several cancers, including pediatric kidney cancer. Our data are the first to indicate vulnerability of human ME methylation establishment to TS exposure, with a general trend of increasing levels of methylation at these loci. Further investigation is needed to determine how TS exposure-mediated changes in DNA methylation at MEs, and consequent expression levels, might affect smoking-related disease risk.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2022-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48510620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-16eCollection Date: 2022-01-01DOI: 10.1093/eep/dvac001
Eric E Nilsson, Millissia Ben Maamar, Michael K Skinner
Many environmental toxicants have been shown to be associated with the transgenerational inheritance of increased disease susceptibility. This review describes the generational toxicity of some of these chemicals and their role in the induction of epigenetic transgenerational inheritance of disease. Epigenetic factors include DNA methylation, histone modifications, retention of histones in sperm, changes to chromatin structure, and expression of non-coding RNAs. For toxicant-induced epigenetic transgenerational inheritance to occur, exposure to a toxicant must result in epigenetic changes to germ cells (sperm or eggs) since it is the germ cells that carry molecular information to subsequent generations. In addition, the epigenetic changes induced in transgenerational generation animals must cause alterations in gene expression in these animals' somatic cells. In some cases of generational toxicology, negligible changes are seen in the directly exposed generations, but increased disease rates are seen in transgenerational descendants. Governmental policies regulating toxicant exposure should take generational effects into account. A new approach that takes into consideration generational toxicity will be needed to protect our future populations.
{"title":"Role of epigenetic transgenerational inheritance in generational toxicology.","authors":"Eric E Nilsson, Millissia Ben Maamar, Michael K Skinner","doi":"10.1093/eep/dvac001","DOIUrl":"https://doi.org/10.1093/eep/dvac001","url":null,"abstract":"<p><p>Many environmental toxicants have been shown to be associated with the transgenerational inheritance of increased disease susceptibility. This review describes the generational toxicity of some of these chemicals and their role in the induction of epigenetic transgenerational inheritance of disease. Epigenetic factors include DNA methylation, histone modifications, retention of histones in sperm, changes to chromatin structure, and expression of non-coding RNAs. For toxicant-induced epigenetic transgenerational inheritance to occur, exposure to a toxicant must result in epigenetic changes to germ cells (sperm or eggs) since it is the germ cells that carry molecular information to subsequent generations. In addition, the epigenetic changes induced in transgenerational generation animals must cause alterations in gene expression in these animals' somatic cells. In some cases of generational toxicology, negligible changes are seen in the directly exposed generations, but increased disease rates are seen in transgenerational descendants. Governmental policies regulating toxicant exposure should take generational effects into account. A new approach that takes into consideration generational toxicity will be needed to protect our future populations.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cf/2c/dvac001.PMC8848501.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39648584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Golding, M. Pembrey, Steven Gregory, M. Suderman, Yasmin Iles-Caven, K. Northstone
Abstract Although there are many examples in the experimental literature of an environmental exposure in one generation impacting the phenotypes of subsequent generations, there are few studies that can assess whether such associations occur in humans. The Avon Longitudinal Study of Parents and Children (ALSPAC) has, however, been able to determine whether there are associations between grandparental exposures and their grandchildren’s development. Several of our studies, including sensitivity to loud noise, have shown associations between a grandmother smoking in pregnancy and the phenotype of the grandchild. These results were mostly specific to the sex of the grandchild and to whether the prenatal (i.e. during pregnancy) smoking occurred in the maternal or paternal grandmother. Here, we have used ancestral data on prenatal smoking among the grandmothers of the ALSPAC index children to examine possible effects on the grandchild’s ability to detect the bitter taste of PROP (6 n-propylthiouracil), distinguishing between the 10% deemed ‘extreme tasters’, and the rest of the population (total N = 4656 children). We showed that grandchildren whose paternal (but not maternal) grandmothers had smoked in pregnancy were more likely than those of non-smoking grandmothers to be extreme tasters [odds ratio (OR) 1.28; 95% confidence interval (CI) 1.03, 1.59] and that this was more likely in granddaughters (OR 1.42; 95% CI 1.03, 1.95) than grandsons (OR 1.18; 95% CI 0.88, 1.60). This pattern of association between paternal foetal exposure and the granddaughter’s development has been found with several other outcomes, suggesting that investigations should be undertaken to investigate possible mechanisms.
{"title":"Paternal grandmother’s smoking in pregnancy is associated with extreme aversion to bitter taste in their grandchildren","authors":"J. Golding, M. Pembrey, Steven Gregory, M. Suderman, Yasmin Iles-Caven, K. Northstone","doi":"10.1093/eep/dvac003","DOIUrl":"https://doi.org/10.1093/eep/dvac003","url":null,"abstract":"Abstract Although there are many examples in the experimental literature of an environmental exposure in one generation impacting the phenotypes of subsequent generations, there are few studies that can assess whether such associations occur in humans. The Avon Longitudinal Study of Parents and Children (ALSPAC) has, however, been able to determine whether there are associations between grandparental exposures and their grandchildren’s development. Several of our studies, including sensitivity to loud noise, have shown associations between a grandmother smoking in pregnancy and the phenotype of the grandchild. These results were mostly specific to the sex of the grandchild and to whether the prenatal (i.e. during pregnancy) smoking occurred in the maternal or paternal grandmother. Here, we have used ancestral data on prenatal smoking among the grandmothers of the ALSPAC index children to examine possible effects on the grandchild’s ability to detect the bitter taste of PROP (6 n-propylthiouracil), distinguishing between the 10% deemed ‘extreme tasters’, and the rest of the population (total N = 4656 children). We showed that grandchildren whose paternal (but not maternal) grandmothers had smoked in pregnancy were more likely than those of non-smoking grandmothers to be extreme tasters [odds ratio (OR) 1.28; 95% confidence interval (CI) 1.03, 1.59] and that this was more likely in granddaughters (OR 1.42; 95% CI 1.03, 1.95) than grandsons (OR 1.18; 95% CI 0.88, 1.60). This pattern of association between paternal foetal exposure and the granddaughter’s development has been found with several other outcomes, suggesting that investigations should be undertaken to investigate possible mechanisms.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43455915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiyi Xu, C. Lindh, T. Fletcher, K. Jakobsson, Karin Engström
Abstract Perfluoroalkyl substances (PFASs) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFASs is via epigenetic changes, such as DNA methylation. Previous studies have evaluated associations between PFAS exposure and DNA methylation among newborns and adults. However, no study has evaluated how PFASs influence DNA methylation among children of school age. In this exploratory study with school-age children exposed to PFASs through drinking water highly contaminated from firefighting foams, we aimed to investigate whether exposure to PFASs was associated with alteration in DNA methylation and epigenetic age acceleration. Sixty-three children aged 7–11 years from the Ronneby Biomarker Cohort (Sweden) were included. The children were either controls with only background exposure (n = 32; perfluorooctane sulfonic acid: median 2.8 and range 1–5 ng/ml) or those exposed to very high levels of PFASs (n = 31; perfluorooctane sulfonic acid: median 295 and range 190–464 ng/ml). These two groups were matched on sex, age, and body mass index. Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip kit. Epigenetic age acceleration was derived from the DNA methylation data. Twelve differentially methylated positions and seven differentially methylated regions were found when comparing the high-exposure group to the control group. There were no differences in epigenetic age acceleration between these two groups (P = 0.66). We found that PFAS exposure was associated with DNA methylation at specific genomic positions and regions in children at school age, which may indicate a possible mechanism for linking PFAS exposure to health effects.
{"title":"Perfluoroalkyl substances influence DNA methylation in school-age children highly exposed through drinking water contaminated from firefighting foam: a cohort study in Ronneby, Sweden","authors":"Yiyi Xu, C. Lindh, T. Fletcher, K. Jakobsson, Karin Engström","doi":"10.1093/eep/dvac004","DOIUrl":"https://doi.org/10.1093/eep/dvac004","url":null,"abstract":"Abstract Perfluoroalkyl substances (PFASs) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFASs is via epigenetic changes, such as DNA methylation. Previous studies have evaluated associations between PFAS exposure and DNA methylation among newborns and adults. However, no study has evaluated how PFASs influence DNA methylation among children of school age. In this exploratory study with school-age children exposed to PFASs through drinking water highly contaminated from firefighting foams, we aimed to investigate whether exposure to PFASs was associated with alteration in DNA methylation and epigenetic age acceleration. Sixty-three children aged 7–11 years from the Ronneby Biomarker Cohort (Sweden) were included. The children were either controls with only background exposure (n = 32; perfluorooctane sulfonic acid: median 2.8 and range 1–5 ng/ml) or those exposed to very high levels of PFASs (n = 31; perfluorooctane sulfonic acid: median 295 and range 190–464 ng/ml). These two groups were matched on sex, age, and body mass index. Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip kit. Epigenetic age acceleration was derived from the DNA methylation data. Twelve differentially methylated positions and seven differentially methylated regions were found when comparing the high-exposure group to the control group. There were no differences in epigenetic age acceleration between these two groups (P = 0.66). We found that PFAS exposure was associated with DNA methylation at specific genomic positions and regions in children at school age, which may indicate a possible mechanism for linking PFAS exposure to health effects.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44821357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-03eCollection Date: 2022-01-01DOI: 10.1093/eep/dvab015
Albert Stuart Reece, Gary Kenneth Hulse
With reports from Australia, Canada, USA, Hawaii and Colorado documenting a link between cannabis and congenital anomalies (CAs), this relationship was investigated in Europe. Data on 90 CAs were accessed from Eurocat. Tobacco and alcohol consumption and median household income data were from the World Bank. Amphetamine, cocaine and last month and daily use of cannabis from the European Monitoring Centre for Drugs and Drug Addiction. Cannabis herb and resin Δ9-tetrahydrocannabinol concentrations were from published reports. Data were processed in R. Twelve thousand three hundred sixty CA rates were sourced across 16 nations of Europe. Nations with a higher or increasing rate of daily cannabis use had a 71.77% higher median CA rates than others [median ± interquartile range 2.13 (0.59, 6.30) v. 1.24 (0.15, 5.14)/10 000 live births (P = 4.74 × 10-17; minimum E-value (mEV) = 1.52]. Eighty-nine out of 90 CAs in bivariate association and 74/90 CAs in additive panel inverse probability weighted space-time regression were cannabis related. In inverse probability weighted interactive panel models lagged to zero, two, four and six years, 76, 31, 50 and 29 CAs had elevated mEVs (< 2.46 × 1039) for cannabis metrics. Cardiovascular, central nervous, gastrointestinal, genital, uronephrology, limb, face and chromosomalgenetic systems along with the multisystem VACTERL syndrome were particularly vulnerable targets. Data reveal that cannabis is related to many CAs and fulfil epidemiological criteria of causality. The triple convergence of rising cannabis use prevalence, intensity of daily use and Δ9-tetrahydrocannabinol concentration in herb and resin is powerfully implicated as a primary driver of European teratogenicity, confirming results from elsewhere.
{"title":"Cannabinoid and substance relationships of European congenital anomaly patterns: a space-time panel regression and causal inferential study.","authors":"Albert Stuart Reece, Gary Kenneth Hulse","doi":"10.1093/eep/dvab015","DOIUrl":"https://doi.org/10.1093/eep/dvab015","url":null,"abstract":"<p><p>With reports from Australia, Canada, USA, Hawaii and Colorado documenting a link between cannabis and congenital anomalies (CAs), this relationship was investigated in Europe. Data on 90 CAs were accessed from Eurocat. Tobacco and alcohol consumption and median household income data were from the World Bank. Amphetamine, cocaine and last month and daily use of cannabis from the European Monitoring Centre for Drugs and Drug Addiction. Cannabis herb and resin Δ9-tetrahydrocannabinol concentrations were from published reports. Data were processed in R. Twelve thousand three hundred sixty CA rates were sourced across 16 nations of Europe. Nations with a higher or increasing rate of daily cannabis use had a 71.77% higher median CA rates than others [median ± interquartile range 2.13 (0.59, 6.30) v. 1.24 (0.15, 5.14)/10 000 live births (<i>P</i> = 4.74 × 10<sup>-17</sup>; minimum <i>E</i>-value (mEV) = 1.52]. Eighty-nine out of 90 CAs in bivariate association and 74/90 CAs in additive panel inverse probability weighted space-time regression were cannabis related. In inverse probability weighted interactive panel models lagged to zero, two, four and six years, 76, 31, 50 and 29 CAs had elevated mEVs (< 2.46 × 10<sup>39</sup>) for cannabis metrics. Cardiovascular, central nervous, gastrointestinal, genital, uronephrology, limb, face and chromosomalgenetic systems along with the multisystem VACTERL syndrome were particularly vulnerable targets. Data reveal that cannabis is related to many CAs and fulfil epidemiological criteria of causality. The triple convergence of rising cannabis use prevalence, intensity of daily use and Δ9-tetrahydrocannabinol concentration in herb and resin is powerfully implicated as a primary driver of European teratogenicity, confirming results from elsewhere.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/18/dvab015.PMC8824558.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39613426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-02eCollection Date: 2022-01-01DOI: 10.1093/eep/dvac002
Shakiba Eslamimehr, A Daniel Jones, Thilani M Anthony, S Hasan Arshad, John W Holloway, Susan Ewart, Rui Luo, Nandini Mukherjee, Parnian Kheirkhah Rahimabad, Su Chen, Wilfried Karmaus
Acetaminophen is used by nearly two-thirds of pregnant women. Although considered safe, studies have demonstrated associations between prenatal acetaminophen use and adverse health outcomes in offspring. Since DNA methylation (DNAm) at birth may act as an early indicator of later health, assessments on whether DNAm of newborns is associated with gestational acetaminophen use or its metabolites are needed. Using data from three consecutive generations of the Isle of Wight cohort (F0-grandmothers, F1-mothers, and F2-offspring) we investigated associations between acetaminophen metabolites in F0 serum at delivery with epigenome-wide DNAm in F1 (Guthrie cards) and between acetaminophen use of F1 and F2-cord-serum levels with F2 cord blood DNAm. In epigenome-wide screening, we eliminated non-informative DNAm sites followed by linear regression of informative sites. Based on repeated pregnancies, indication bias analyses tested whether acetaminophen indicated maternal diseases or has a risk in its own right. Considering that individuals with similar intake process acetaminophen differently, metabolites were clustered to distinguish metabolic exposures. Finally, metabolite clusters from F1-maternal and F2-cord sera were tested for their associations with newborn DNAm (F1 and F2). Twenty-one differential DNAm sites in cord blood were associated with reported maternal acetaminophen intake in the F2 generation. For 11 of these cytosine-phosphate-guanine (CpG) sites, an indication bias was excluded and five were replicated in F2 with metabolite clusters. In addition, metabolite clusters showed associations with 25 CpGs in the F0-F1 discovery analysis, of which five CpGs were replicated in the F2-generation. Our results suggest that prenatal acetaminophen use, measured as metabolites, may influence DNAm in newborns.
{"title":"Association of prenatal acetaminophen use and acetaminophen metabolites with DNA methylation of newborns: analysis of two consecutive generations of the Isle of Wight birth cohort.","authors":"Shakiba Eslamimehr, A Daniel Jones, Thilani M Anthony, S Hasan Arshad, John W Holloway, Susan Ewart, Rui Luo, Nandini Mukherjee, Parnian Kheirkhah Rahimabad, Su Chen, Wilfried Karmaus","doi":"10.1093/eep/dvac002","DOIUrl":"https://doi.org/10.1093/eep/dvac002","url":null,"abstract":"<p><p>Acetaminophen is used by nearly two-thirds of pregnant women. Although considered safe, studies have demonstrated associations between prenatal acetaminophen use and adverse health outcomes in offspring. Since DNA methylation (DNAm) at birth may act as an early indicator of later health, assessments on whether DNAm of newborns is associated with gestational acetaminophen use or its metabolites are needed. Using data from three consecutive generations of the Isle of Wight cohort (F0-grandmothers, F1-mothers, and F2-offspring) we investigated associations between acetaminophen metabolites in F0 serum at delivery with epigenome-wide DNAm in F1 (Guthrie cards) and between acetaminophen use of F1 and F2-cord-serum levels with F2 cord blood DNAm. In epigenome-wide screening, we eliminated non-informative DNAm sites followed by linear regression of informative sites. Based on repeated pregnancies, indication bias analyses tested whether acetaminophen indicated maternal diseases or has a risk in its own right. Considering that individuals with similar intake process acetaminophen differently, metabolites were clustered to distinguish metabolic exposures. Finally, metabolite clusters from F1-maternal and F2-cord sera were tested for their associations with newborn DNAm (F1 and F2). Twenty-one differential DNAm sites in cord blood were associated with reported maternal acetaminophen intake in the F2 generation. For 11 of these cytosine-phosphate-guanine (CpG) sites, an indication bias was excluded and five were replicated in F2 with metabolite clusters. In addition, metabolite clusters showed associations with 25 CpGs in the F0-F1 discovery analysis, of which five CpGs were replicated in the F2-generation. Our results suggest that prenatal acetaminophen use, measured as metabolites, may influence DNAm in newborns.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933617/pdf/dvac002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40313469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}