Pub Date : 2020-11-18eCollection Date: 2020-01-01DOI: 10.1093/eep/dvaa015
Stephanie O M Dyke, Catherine A Ennis, Yann Joly, Jörn Walter, Reiner Siebert, Tomi Pastinen
Given the public interest in epigenetic science, this study aimed to better understand media representations of epigenetics in national newspaper coverage in various regions in North America, Europe, and Asia. Content analysis was used to study media messages about epigenetics, their policy focus, and the balance of the reporting. We identified several recurring themes in the news reports, including policy messages relating to individual and societal responsibilities. We also found shortcomings in the media's portrayal of epigenetic science, and sought to identify potential causes by considering the underlying scientific evidence that the media reported on. A case study analysis showed that the results of epigenetic studies were often overstated in academic research publications due to common experimental limitations. We suggest that defining standardized criteria with which to evaluate epigenetic studies could help to overcome some of the challenges inherent in translating complex epigenetic research findings for non-technical audiences, and present a Press Kit template that researchers can adapt and use to aid in the development of accurate and balanced press releases.
{"title":"Communicating science: epigenetics in the spotlight.","authors":"Stephanie O M Dyke, Catherine A Ennis, Yann Joly, Jörn Walter, Reiner Siebert, Tomi Pastinen","doi":"10.1093/eep/dvaa015","DOIUrl":"https://doi.org/10.1093/eep/dvaa015","url":null,"abstract":"<p><p>Given the public interest in epigenetic science, this study aimed to better understand media representations of epigenetics in national newspaper coverage in various regions in North America, Europe, and Asia. Content analysis was used to study media messages about epigenetics, their policy focus, and the balance of the reporting. We identified several recurring themes in the news reports, including policy messages relating to individual and societal responsibilities. We also found shortcomings in the media's portrayal of epigenetic science, and sought to identify potential causes by considering the underlying scientific evidence that the media reported on. A case study analysis showed that the results of epigenetic studies were often overstated in academic research publications due to common experimental limitations. We suggest that defining standardized criteria with which to evaluate epigenetic studies could help to overcome some of the challenges inherent in translating complex epigenetic research findings for non-technical audiences, and present a Press Kit template that researchers can adapt and use to aid in the development of accurate and balanced press releases.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38642804","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}
The dynamic patterning of DNA and histone methylation during oocyte development presents a potentially susceptible time for epigenetic disruption due to early life environmental exposure of future mothers. We investigated whether maternal exposure to folic acid deficient and supplemented diets starting in utero could affect oocytes and cause adverse developmental and epigenetic effects in next generation progeny. Female BALB/c mice (F0) were placed on one of four amino acid defined diets for 4 weeks before pregnancy and throughout gestation and lactation: folic acid control (rodent recommended daily intake; Ctrl), 7-fold folic acid deficient, 10-fold folic acid supplemented or 20-fold folic acid supplemented diets. F1 female pups were weaned onto Ctrl diets, mated to produce the F2 generation and the F2 offspring were examined at E18.5 for developmental and epigenetic abnormalities. Resorption rates were increased and litter sizes decreased amongst F2 E18.5-day litters in the 20-fold folic acid supplemented group. Increases in abnormal embryo outcomes were observed in all three folic acid deficient and supplemented groups. Subtle genome-wide DNA methylation alterations were found in the placentas and brains of F2 offspring in the 7-fold folic acid deficient , 10-fold folic acid supplemented and 20-fold folic acid supplemented groups; in contrast, global and imprinted gene methylation were not affected. The findings show that early life female environmental exposures to both low and high folate prior to oocyte maturation can compromise oocyte quality, adversely affecting offspring of the next generation, in part by altering DNA methylation patterns.
{"title":"Impact of mothers' early life exposure to low or high folate on progeny outcome and DNA methylation patterns.","authors":"Lundi Ly, Donovan Chan, Mylène Landry, Camille Angle, Josée Martel, Jacquetta Trasler","doi":"10.1093/eep/dvaa018","DOIUrl":"https://doi.org/10.1093/eep/dvaa018","url":null,"abstract":"<p><p>The dynamic patterning of DNA and histone methylation during oocyte development presents a potentially susceptible time for epigenetic disruption due to early life environmental exposure of future mothers. We investigated whether maternal exposure to folic acid deficient and supplemented diets starting <i>in utero</i> could affect oocytes and cause adverse developmental and epigenetic effects in next generation progeny. Female BALB/c mice (F0) were placed on one of four amino acid defined diets for 4 weeks before pregnancy and throughout gestation and lactation: folic acid control (rodent recommended daily intake; Ctrl), 7-fold folic acid deficient, 10-fold folic acid supplemented or 20-fold folic acid supplemented diets. F1 female pups were weaned onto Ctrl diets, mated to produce the F2 generation and the F2 offspring were examined at E18.5 for developmental and epigenetic abnormalities. Resorption rates were increased and litter sizes decreased amongst F2 E18.5-day litters in the 20-fold folic acid supplemented group. Increases in abnormal embryo outcomes were observed in all three folic acid deficient and supplemented groups. Subtle genome-wide DNA methylation alterations were found in the placentas and brains of F2 offspring in the 7-fold folic acid deficient , 10-fold folic acid supplemented and 20-fold folic acid supplemented groups; in contrast, global and imprinted gene methylation were not affected. The findings show that early life female environmental exposures to both low and high folate prior to oocyte maturation can compromise oocyte quality, adversely affecting offspring of the next generation, in part by altering DNA methylation patterns.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38642805","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 : 2020-10-03eCollection Date: 2020-01-01DOI: 10.1093/eep/dvaa013
Marthe Behrends, Olivia Engmann
Human histone H1.5, in mice called H1b, belongs to the family of linker histones (H1), which are key players in chromatin organization. These proteins sit on top of nucleosomes, in part to stabilize them, and recruit core histone modifying enzymes. Through subtype-specific deposition patterns and numerous post-translational modifications, they fine-tune gene expression and chromatin architecture, and help to control cell fate and homeostasis. However, even though it is increasingly implicated in mammalian development, H1.5 has not received as much research attention as its relatives. Recent studies have focused on its prognostic value in cancer patients and its contribution to tumorigenesis through specific molecular mechanisms. However, many functions of H1.5 are still poorly understood. In this review, we will summarize what is currently known about H1.5 and its function in cell differentiation and carcinogenesis. We will suggest key experiments that are required to understand the molecular network, in which H1.5 is embedded. These experiments will advance our understanding of the epigenetic reprogramming occurring in developmental and carcinogenic processes.
{"title":"Linker histone H1.5 is an underestimated factor in differentiation and carcinogenesis.","authors":"Marthe Behrends, Olivia Engmann","doi":"10.1093/eep/dvaa013","DOIUrl":"https://doi.org/10.1093/eep/dvaa013","url":null,"abstract":"<p><p>Human histone H1.5, in mice called H1b, belongs to the family of linker histones (H1), which are key players in chromatin organization. These proteins sit on top of nucleosomes, in part to stabilize them, and recruit core histone modifying enzymes. Through subtype-specific deposition patterns and numerous post-translational modifications, they fine-tune gene expression and chromatin architecture, and help to control cell fate and homeostasis. However, even though it is increasingly implicated in mammalian development, H1.5 has not received as much research attention as its relatives. Recent studies have focused on its prognostic value in cancer patients and its contribution to tumorigenesis through specific molecular mechanisms. However, many functions of H1.5 are still poorly understood. In this review, we will summarize what is currently known about H1.5 and its function in cell differentiation and carcinogenesis. We will suggest key experiments that are required to understand the molecular network, in which H1.5 is embedded. These experiments will advance our understanding of the epigenetic reprogramming occurring in developmental and carcinogenic processes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38729659","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}
Anticipatory effects mediated by epigenetic changes occur when parents modify the phenotype of their offspring by making epigenetic changes in their gametes guided by information from an environmental cue. To investigate when do anticipatory effects mediated by epigenetic changes evolve in a fluctuating environment, I use an individual based simulation model with explicit genetic architecture. The model allows for the population to respond to environmental changes by evolving plasticity, bet-hedging, or by tracking the environment with genetic adaptation, in addition to the evolution of anticipatory effects. The results show that anticipatory effects evolve when the environmental cue provides reliable information about the environment and the environment changes at intermediate rates, provided that fitness costs of anticipatory effects are rather low. Moreover, evolution of anticipatory effects is quite robust to different genetic architectures when reliability of the environmental cue is high. Anticipatory effects always give smaller fitness benefits than within generation plasticity, suggesting a possible reason for generally small observed anticipatory effects in empirical studies.
{"title":"Evolution of anticipatory effects mediated by epigenetic changes","authors":"Ilkka Kronholm","doi":"10.1093/eep/dvac007","DOIUrl":"https://doi.org/10.1093/eep/dvac007","url":null,"abstract":"Anticipatory effects mediated by epigenetic changes occur when parents modify the phenotype of their offspring by making epigenetic changes in their gametes guided by information from an environmental cue. To investigate when do anticipatory effects mediated by epigenetic changes evolve in a fluctuating environment, I use an individual based simulation model with explicit genetic architecture. The model allows for the population to respond to environmental changes by evolving plasticity, bet-hedging, or by tracking the environment with genetic adaptation, in addition to the evolution of anticipatory effects. The results show that anticipatory effects evolve when the environmental cue provides reliable information about the environment and the environment changes at intermediate rates, provided that fitness costs of anticipatory effects are rather low. Moreover, evolution of anticipatory effects is quite robust to different genetic architectures when reliability of the environmental cue is high. Anticipatory effects always give smaller fitness benefits than within generation plasticity, suggesting a possible reason for generally small observed anticipatory effects in empirical studies.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44956636","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 : 2020-09-27eCollection Date: 2020-01-01DOI: 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。
{"title":"TCDD-induced multi- and transgenerational changes in the methylome of male zebrafish gonads.","authors":"Camille Akemann, Danielle N Meyer, Katherine Gurdziel, Tracie R Baker","doi":"10.1093/eep/dvaa010","DOIUrl":"10.1093/eep/dvaa010","url":null,"abstract":"<p><p>The legacy endocrine disrupting chemical and aryl hydrocarbon receptor agonist, 2,3,7,8-tetrachlorodibenzo-<i>p</i>-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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/09/90/dvaa010.PMC7660120.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38729658","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 : 2020-09-27eCollection Date: 2020-01-01DOI: 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.
{"title":"Gestational exposure to particulate air pollution exacerbates the growth phenotypes induced by preconception paternal alcohol use: a multiplex model of exposure.","authors":"Toriq A Mustapha, Richard C Chang, Dennis Garcia-Rhodes, Drew Pendleton, Natalie M Johnson, Michael C Golding","doi":"10.1093/eep/dvaa011","DOIUrl":"https://doi.org/10.1093/eep/dvaa011","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38729657","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 : 2020-07-18eCollection Date: 2020-01-01DOI: 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。
{"title":"General anesthesia, germ cells and the missing heritability of autism: an urgent need for research.","authors":"Jill Escher, La Donna Ford","doi":"10.1093/eep/dvaa007","DOIUrl":"10.1093/eep/dvaa007","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2020-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38185353","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 : 2020-07-18eCollection Date: 2020-01-01DOI: 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.
{"title":"Transgenerational epigenetic reprogramming of early embryos: a mechanistic model.","authors":"Corrado Spadafora","doi":"10.1093/eep/dvaa009","DOIUrl":"https://doi.org/10.1093/eep/dvaa009","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38185354","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 : 2020-07-07eCollection Date: 2020-01-01DOI: 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.
{"title":"DNA methylation reprogramming in medaka fish, a promising animal model for environmental epigenetics research.","authors":"Xuegeng Wang, Ramji K Bhandari","doi":"10.1093/eep/dvaa008","DOIUrl":"https://doi.org/10.1093/eep/dvaa008","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38164615","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 : 2020-06-14eCollection Date: 2020-01-01DOI: 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.
{"title":"Epigenetic biomarkers and preterm birth.","authors":"Bongsoo Park, Rasheda Khanam, Vinesh Vinayachandran, Abdullah H Baqui, Stephanie J London, Shyam Biswal","doi":"10.1093/eep/dvaa005","DOIUrl":"10.1093/eep/dvaa005","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38057360","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}