首页 > 最新文献

Environmental Epigenetics最新文献

英文 中文
Environmental Epigenetics update. 环境表观遗传学更新。
IF 3.8 Q1 Environmental Science Pub Date : 2021-04-08 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab001
Michael K Skinner
Environmental Epigenetics, an Oxford University Press publication, just initiated its seventh year of operations with this Volume 7 Issue 1. We are a completely 100% Open Access journal listed in PMC and PubMed, along with numerous other access sites. Environmental Epigenetics initiated its review to obtain an impact factor in 2020 and hope to receive this over the next year. Special issues have occurred each year and we encourage requests for special issues in environmental epigenetics. Our Special Issue in 2020 was on Epigenetic Transgenerational Inheritance involving 21 manuscripts (https://academic.oup. com/eep/pages/special_issues). The amount and diversity of our published studies is 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":"<i>Environmental Epigenetics</i> update.","authors":"Michael K Skinner","doi":"10.1093/eep/dvab001","DOIUrl":"https://doi.org/10.1093/eep/dvab001","url":null,"abstract":"Environmental Epigenetics, an Oxford University Press publication, just initiated its seventh year of operations with this Volume 7 Issue 1. We are a completely 100% Open Access journal listed in PMC and PubMed, along with numerous other access sites. Environmental Epigenetics initiated its review to obtain an impact factor in 2020 and hope to receive this over the next year. Special issues have occurred each year and we encourage requests for special issues in environmental epigenetics. Our Special Issue in 2020 was on Epigenetic Transgenerational Inheritance involving 21 manuscripts (https://academic.oup. com/eep/pages/special_issues). The amount and diversity of our published studies is 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":"2021-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvab001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38811537","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}
引用次数: 0
Ancestral plastics exposure induces transgenerational disease-specific sperm epigenome-wide association biomarkers. 祖先塑料暴露诱导跨代疾病特异性精子表观基因组关联生物标志物。
IF 3.8 Q1 Environmental Science Pub Date : 2021-03-20 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvaa023
Jennifer L M Thorson, Daniel Beck, Millissia Ben Maamar, Eric E Nilsson, Michael K Skinner

Plastic-derived compounds are one of the most frequent daily worldwide exposures. Previously a mixture of plastic-derived toxicants composed of bisphenol A, bis(2-ethylhexyl) phthalate, and dibutyl phthalate at low-dose exposures of a gestating female rats was found to promote the epigenetic transgenerational inheritance of disease to the offspring (F1 generation), grand-offspring (F2 generation), and great-grand-offspring (F3 generation). Epigenetic analysis of the male sperm was found to result in differential DNA methylation regions (DMRs) in the transgenerational F3 generation male sperm. The current study is distinct and was designed to use an epigenome-wide association study to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations indicate disease-specific DMRs called epimutations in the transgenerational F3 generation great-grand-offspring of rats ancestrally exposed to plastics. The epigenetic DMR biomarkers were identified for testis disease, kidney disease, and multiple (≥2) diseases. These disease sperm epimutation biomarkers were found to be predominantly disease-specific. The genomic locations and features of these DMRs were identified. Interestingly, the disease-specific DMR-associated genes were previously shown to be linked with each of the specific diseases. Therefore, the germline has ancestrally derived epimutations that potentially transmit transgenerational disease susceptibilities. Epigenetic biomarkers for specific diseases could be used as diagnostics to facilitate clinical management of disease and preventative medicine.

塑料衍生化合物是世界范围内最常见的日常暴露之一。先前发现,由双酚a、双(2-乙基己基)邻苯二甲酸酯和邻苯二甲酸二丁酯组成的塑料衍生毒物的混合物在低剂量暴露于妊娠雌性大鼠时,可促进疾病对后代(F1代)、后代(F2代)和曾祖后代(F3代)的表观遗传跨代遗传。对男性精子的表观遗传分析发现,在跨代F3代男性精子中存在差异的DNA甲基化区域(DMRs)。目前的研究是独特的,旨在使用全表观基因组关联研究来识别特定跨代疾病的潜在精子DNA甲基化生物标志物。观察结果表明,在祖上接触塑料的大鼠的跨代F3代曾孙后代中,被称为表观突变的疾病特异性dmr。发现了睾丸疾病、肾脏疾病和多种(≥2)疾病的表观遗传DMR生物标志物。发现这些疾病精子上皮化生物标志物主要是疾病特异性的。确定了这些DMRs的基因组位置和特征。有趣的是,疾病特异性dmr相关基因先前被证明与每种特定疾病有关。因此,种系具有可能传递跨代疾病易感性的祖先衍生变异。特定疾病的表观遗传生物标志物可作为诊断手段,促进疾病的临床管理和预防医学。
{"title":"Ancestral plastics exposure induces transgenerational disease-specific sperm epigenome-wide association biomarkers.","authors":"Jennifer L M Thorson,&nbsp;Daniel Beck,&nbsp;Millissia Ben Maamar,&nbsp;Eric E Nilsson,&nbsp;Michael K Skinner","doi":"10.1093/eep/dvaa023","DOIUrl":"https://doi.org/10.1093/eep/dvaa023","url":null,"abstract":"<p><p>Plastic-derived compounds are one of the most frequent daily worldwide exposures. Previously a mixture of plastic-derived toxicants composed of bisphenol A, bis(2-ethylhexyl) phthalate, and dibutyl phthalate at low-dose exposures of a gestating female rats was found to promote the epigenetic transgenerational inheritance of disease to the offspring (F1 generation), grand-offspring (F2 generation), and great-grand-offspring (F3 generation). Epigenetic analysis of the male sperm was found to result in differential DNA methylation regions (DMRs) in the transgenerational F3 generation male sperm. The current study is distinct and was designed to use an epigenome-wide association study to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations indicate disease-specific DMRs called epimutations in the transgenerational F3 generation great-grand-offspring of rats ancestrally exposed to plastics. The epigenetic DMR biomarkers were identified for testis disease, kidney disease, and multiple (≥2) diseases. These disease sperm epimutation biomarkers were found to be predominantly disease-specific. The genomic locations and features of these DMRs were identified. Interestingly, the disease-specific DMR-associated genes were previously shown to be linked with each of the specific diseases. Therefore, the germline has ancestrally derived epimutations that potentially transmit transgenerational disease susceptibilities. Epigenetic biomarkers for specific diseases could be used as diagnostics to facilitate clinical management of disease and preventative medicine.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25581214","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}
引用次数: 11
Effect of concentration and duration of particulate matter exposure on the transcriptome and DNA methylome of bronchial epithelial cells. 颗粒物暴露浓度和持续时间对支气管上皮细胞转录组和DNA甲基化的影响。
IF 3.8 Q1 Environmental Science Pub Date : 2021-02-28 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvaa022
Steven K Huang, Priya Tripathi, Lada A Koneva, Raymond G Cavalcante, Nathan Craig, Anne M Scruggs, Maureen A Sartor, Furong Deng, Yahong Chen

Exposure to particulate matter (PM) from ambient air pollution is a well-known risk factor for many lung diseases, but the mechanism(s) for this is not completely understood. Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (<2.5 µm) PM (PM2.5). Although some of these changes have been reported in other studies, a comparison of how different concentrations and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. Here, we exposed BEAS-2B, a bronchial epithelial cell line, to different concentrations of PM2.5, and compared how single or repeated doses of PM2.5 affect both the transcriptome and methylome of cells. Widespread changes in gene expression occurred after cells were exposed to a single treatment of high-concentration (30 µg/cm2) PM2.5 for 24 h. These genes were enriched in pathways regulating cytokine-cytokine interactions, Mitogen-Activated Protein Kinase (MAPK) signaling, PI3K-Akt signaling, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes, with just a slightly greater trend toward overall hypomethylation across the genome. Cells exposed to a lower concentration (1 µg/cm2) of PM2.5 demonstrated a comparable, but more attenuated change in gene expression compared to cells exposed to higher concentrations. There were also many genes affected by lower concentrations of PM2.5, but not higher concentrations. Additionally, repeated exposure to PM2.5 (1 µg/cm2) for seven days resulted in transcriptomic and DNA methylomic changes that were distinct from cells treated with PM2.5 for only one day. Compared to single exposure, repeated exposure to PM2.5 caused a more notable degree of hypomethylation across the genome, though certain genes and regions demonstrated increased DNA methylation. The overall increase in hypomethylation, especially with repeated exposure to PM2.5, was associated with an increase in expression of ten-eleven translocation enzymes. These data demonstrate how variations in concentration and duration of PM2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells, which may have important implications in the development of both acute and chronic lung disease.

暴露于来自环境空气污染的颗粒物(PM)是许多肺部疾病的一个众所周知的危险因素,但其机制尚不完全清楚。支气管上皮细胞排列在呼吸道的气道上,在基因表达和DNA甲基化方面发生全基因组水平的变化,特别是当暴露于细颗粒物时(2.5)。尽管在其他研究中已经报道了其中的一些变化,但尚未对不同浓度和暴露时间如何影响基因转录组和DNA甲基化组进行比较。在这里,我们将支气管上皮细胞系BEAS-2B暴露于不同浓度的PM2.5中,并比较了单次或重复剂量的PM2.5如何影响细胞的转录组和甲基组。细胞暴露于高浓度(30µg/cm2) PM2.5单次处理24小时后,基因表达发生了广泛的变化。这些基因在调节细胞因子-细胞因子相互作用、丝裂原活化蛋白激酶(MAPK)信号通路、PI3K-Akt信号通路、IL6和P53的通路中富集。DNA甲基化分析显示,近一半的差异表达基因也有DNA甲基化变化,只是整个基因组的整体低甲基化趋势略大。与暴露于较高浓度的细胞相比,暴露于较低浓度(1µg/cm2) PM2.5的细胞表现出类似但更减弱的基因表达变化。还有许多基因受到PM2.5浓度较低而不是较高的影响。此外,重复暴露于PM2.5(1µg/cm2) 7天导致转录组和DNA甲基化变化,与仅暴露于PM2.5 1天的细胞不同。与单次暴露相比,反复暴露在PM2.5中导致整个基因组的低甲基化程度更显著,尽管某些基因和区域显示出DNA甲基化增加。低甲基化的总体增加,特别是反复暴露于PM2.5中,与10 - 11易位酶的表达增加有关。这些数据表明PM2.5暴露浓度和持续时间的变化如何诱导支气管上皮细胞转录组和DNA甲基化谱的明显差异,这可能在急性和慢性肺部疾病的发展中具有重要意义。
{"title":"Effect of concentration and duration of particulate matter exposure on the transcriptome and DNA methylome of bronchial epithelial cells.","authors":"Steven K Huang,&nbsp;Priya Tripathi,&nbsp;Lada A Koneva,&nbsp;Raymond G Cavalcante,&nbsp;Nathan Craig,&nbsp;Anne M Scruggs,&nbsp;Maureen A Sartor,&nbsp;Furong Deng,&nbsp;Yahong Chen","doi":"10.1093/eep/dvaa022","DOIUrl":"https://doi.org/10.1093/eep/dvaa022","url":null,"abstract":"<p><p>Exposure to particulate matter (PM) from ambient air pollution is a well-known risk factor for many lung diseases, but the mechanism(s) for this is not completely understood. Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (<2.5 µm) PM (PM<sub>2.5</sub>). Although some of these changes have been reported in other studies, a comparison of how different concentrations and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. Here, we exposed BEAS-2B, a bronchial epithelial cell line, to different concentrations of PM<sub>2.5</sub>, and compared how single or repeated doses of PM<sub>2.5</sub> affect both the transcriptome and methylome of cells. Widespread changes in gene expression occurred after cells were exposed to a single treatment of high-concentration (30 µg/cm<sup>2</sup>) PM<sub>2.5</sub> for 24 h. These genes were enriched in pathways regulating cytokine-cytokine interactions, Mitogen-Activated Protein Kinase (MAPK) signaling, PI3K-Akt signaling, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes, with just a slightly greater trend toward overall hypomethylation across the genome. Cells exposed to a lower concentration (1 µg/cm<sup>2</sup>) of PM<sub>2.5</sub> demonstrated a comparable, but more attenuated change in gene expression compared to cells exposed to higher concentrations. There were also many genes affected by lower concentrations of PM<sub>2.5</sub>, but not higher concentrations. Additionally, repeated exposure to PM<sub>2.5</sub> (1 µg/cm<sup>2</sup>) for seven days resulted in transcriptomic and DNA methylomic changes that were distinct from cells treated with PM<sub>2.5</sub> for only one day. Compared to single exposure, repeated exposure to PM<sub>2.5</sub> caused a more notable degree of hypomethylation across the genome, though certain genes and regions demonstrated increased DNA methylation. The overall increase in hypomethylation, especially with repeated exposure to PM<sub>2.5</sub>, was associated with an increase in expression of ten-eleven translocation enzymes. These data demonstrate how variations in concentration and duration of PM<sub>2.5</sub> exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells, which may have important implications in the development of both acute and chronic lung disease.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25456841","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}
引用次数: 11
Perinatal DEHP exposure induces sex- and tissue-specific DNA methylation changes in both juvenile and adult mice. 围产期DEHP暴露诱导幼鼠和成年小鼠的性别和组织特异性DNA甲基化变化。
IF 3.8 Q1 Environmental Science Pub Date : 2021-01-01 DOI: 10.1093/eep/dvab004
Siyu Liu, Kai Wang, Laurie K Svoboda, Christine A Rygiel, Kari Neier, Tamara R Jones, Raymond G Cavalcante, Justin A Colacino, Dana C Dolinoy, Maureen A Sartor

Di(2-ethylhexyl) phthalate (DEHP) is a type of phthalate plasticizer found in a variety of consumer products and poses a public health concern due to its metabolic and endocrine disruption activities. Dysregulation of epigenetic modifications, including DNA methylation, has been shown to be an important mechanism for the pathogenic effects of prenatal exposures, including phthalates. In this study, we used an established mouse model to study the effect of perinatal DEHP exposure on the DNA methylation profile in liver (a primary target tissue of DEHP) and blood (a common surrogate tissue) of both juvenile and adult mice. Despite exposure ceasing at 3 weeks of age (PND21), we identified thousands of sex-specific differential DNA methylation events in 5-month old mice, more than identified at PND21, both in blood and liver. Only a small number of these differentially methylated cytosines (DMCs) overlapped between the time points, or between tissues (i.e. liver and blood), indicating blood may not be an appropriate surrogate tissue to estimate the effects of DEHP exposure on liver DNA methylation. We detected sex-specific DMCs common between 3-week and 5-month samples, pointing to specific DNA methylation alterations that are consistent between weanling and adult mice. In summary, this is the first study to assess the genome-wide DNA methylation profiles in liver and blood at two different aged cohorts in response to perinatal DEHP exposure. Our findings cast light on the implications of using surrogate tissue instead of target tissue in human population-based studies and identify epigenetic biomarkers for DEHP exposure.

邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种邻苯二甲酸酯增塑剂,存在于各种消费品中,由于其代谢和内分泌干扰活动而引起公众健康关注。表观遗传修饰的失调,包括DNA甲基化,已被证明是产前暴露(包括邻苯二甲酸盐)致病作用的重要机制。在这项研究中,我们使用已建立的小鼠模型来研究围产期DEHP暴露对幼年和成年小鼠肝脏(DEHP的主要靶组织)和血液(常见替代组织)DNA甲基化谱的影响。尽管暴露在3周龄(PND21)时停止,但我们在5个月大的小鼠血液和肝脏中发现了数千个性别特异性差异DNA甲基化事件,比PND21时发现的要多。只有少数这些差异甲基化的胞嘧啶(dmc)在时间点之间或组织之间(即肝脏和血液)重叠,表明血液可能不是评估DEHP暴露对肝脏DNA甲基化影响的合适替代组织。我们在3周和5个月的样本中检测到性别特异性dmc,指出断奶小鼠和成年小鼠之间的特定DNA甲基化改变是一致的。总之,这是第一项评估围产期DEHP暴露对两组不同年龄人群肝脏和血液中全基因组DNA甲基化谱的影响的研究。我们的研究结果揭示了在基于人群的研究中使用替代组织代替靶组织的意义,并确定了DEHP暴露的表观遗传生物标志物。
{"title":"Perinatal DEHP exposure induces sex- and tissue-specific DNA methylation changes in both juvenile and adult mice.","authors":"Siyu Liu,&nbsp;Kai Wang,&nbsp;Laurie K Svoboda,&nbsp;Christine A Rygiel,&nbsp;Kari Neier,&nbsp;Tamara R Jones,&nbsp;Raymond G Cavalcante,&nbsp;Justin A Colacino,&nbsp;Dana C Dolinoy,&nbsp;Maureen A Sartor","doi":"10.1093/eep/dvab004","DOIUrl":"https://doi.org/10.1093/eep/dvab004","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a type of phthalate plasticizer found in a variety of consumer products and poses a public health concern due to its metabolic and endocrine disruption activities. Dysregulation of epigenetic modifications, including DNA methylation, has been shown to be an important mechanism for the pathogenic effects of prenatal exposures, including phthalates. In this study, we used an established mouse model to study the effect of perinatal DEHP exposure on the DNA methylation profile in liver (a primary target tissue of DEHP) and blood (a common surrogate tissue) of both juvenile and adult mice. Despite exposure ceasing at 3 weeks of age (PND21), we identified thousands of sex-specific differential DNA methylation events in 5-month old mice, more than identified at PND21, both in blood and liver. Only a small number of these differentially methylated cytosines (DMCs) overlapped between the time points, or between tissues (i.e. liver and blood), indicating blood may not be an appropriate surrogate tissue to estimate the effects of DEHP exposure on liver DNA methylation. We detected sex-specific DMCs common between 3-week and 5-month samples, pointing to specific DNA methylation alterations that are consistent between weanling and adult mice. In summary, this is the first study to assess the genome-wide DNA methylation profiles in liver and blood at two different aged cohorts in response to perinatal DEHP exposure. Our findings cast light on the implications of using surrogate tissue instead of target tissue in human population-based studies and identify epigenetic biomarkers for DEHP exposure.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvab004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9544595","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}
引用次数: 7
Short- and long-term effects of perinatal phthalate exposures on metabolic pathways in the mouse liver. 围产期邻苯二甲酸盐暴露对小鼠肝脏代谢途径的短期和长期影响。
IF 3.8 Q1 Environmental Science Pub Date : 2020-12-23 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa017
Kari Neier, Luke Montrose, Kathleen Chen, Maureen A Malloy, Tamara R Jones, Laurie K Svoboda, Craig Harris, Peter X K Song, Subramaniam Pennathur, Maureen A Sartor, Dana C Dolinoy

Phthalates have been demonstrated to interfere with metabolism, presumably by interacting with peroxisome proliferator-activated receptors (PPARs). However, mechanisms linking developmental phthalate exposures to long-term metabolic effects have not yet been elucidated. We investigated the hypothesis that developmental phthalate exposure has long-lasting impacts on PPAR target gene expression and DNA methylation to influence hepatic metabolic profiles across the life course. We utilized an established longitudinal mouse model of perinatal exposures to diethylhexyl phthalate and diisononyl phthalate, and a mixture of diethylhexyl phthalate+diisononyl phthalate. Exposure was through the diet and spanned from 2 weeks before mating until weaning at postnatal day 21 (PND21). Liver tissue was analyzed from the offspring of exposed and control mice at PND21 and in another cohort of exposed and control mice at 10 months of age. RNA-seq and pathway enrichment analyses indicated that acetyl-CoA metabolic processes were altered in diisononyl phthalate-exposed female livers at both PND21 and 10 months (FDR = 0.0018). Within the pathway, all 13 significant genes were potential PPAR target genes. Promoter DNA methylation was altered at three candidate genes, but persistent effects were only observed for Fasn. Targeted metabolomics indicated that phthalate-exposed females had decreased acetyl-CoA at PND21 and increased acetyl-CoA and acylcarnitines at 10 months. Together, our data suggested that perinatal phthalate exposures were associated with short- and long-term activation of PPAR target genes, which manifested as increased fatty acid production in early postnatal life and increased fatty acid oxidation in adulthood. This presents a novel molecular pathway linking developmental phthalate exposures and metabolic health outcomes.

邻苯二甲酸酯已被证明干扰代谢,可能是通过与过氧化物酶体增殖激活受体(ppar)相互作用。然而,将发育中邻苯二甲酸盐暴露与长期代谢影响联系起来的机制尚未阐明。我们研究了一种假设,即发育期邻苯二甲酸盐暴露对PPAR靶基因表达和DNA甲基化具有长期影响,从而影响整个生命过程中的肝脏代谢谱。我们利用建立的纵向小鼠模型,围产期暴露于邻苯二甲酸二乙基己酯和邻苯二甲酸二异壬酯,以及邻苯二甲酸二乙基己酯+邻苯二甲酸二异壬酯的混合物。暴露时间为交配前2周至出生后第21天断奶(PND21)。研究人员分析了PND21时暴露小鼠和对照小鼠的后代以及另一组10月龄暴露小鼠和对照小鼠的肝脏组织。RNA-seq和途径富集分析表明,暴露于邻苯二甲酸二异戊二酯的女性肝脏在PND21和10个月时乙酰辅酶a代谢过程发生了改变(FDR = 0.0018)。在该通路中,13个重要基因均为潜在的PPAR靶基因。三个候选基因的启动子DNA甲基化发生了改变,但只在Fasn上观察到持续的影响。目标代谢组学表明,暴露于邻苯二甲酸盐的雌性在PND21时乙酰辅酶a降低,在10个月时乙酰辅酶a和酰基肉碱增加。总之,我们的数据表明围产期邻苯二甲酸盐暴露与PPAR靶基因的短期和长期激活有关,表现为出生后早期脂肪酸生成增加,成年后脂肪酸氧化增加。这提出了一个新的分子途径连接发育邻苯二甲酸盐暴露和代谢健康结果。
{"title":"Short- and long-term effects of perinatal phthalate exposures on metabolic pathways in the mouse liver.","authors":"Kari Neier, Luke Montrose, Kathleen Chen, Maureen A Malloy, Tamara R Jones, Laurie K Svoboda, Craig Harris, Peter X K Song, Subramaniam Pennathur, Maureen A Sartor, Dana C Dolinoy","doi":"10.1093/eep/dvaa017","DOIUrl":"10.1093/eep/dvaa017","url":null,"abstract":"<p><p>Phthalates have been demonstrated to interfere with metabolism, presumably by interacting with peroxisome proliferator-activated receptors (PPARs). However, mechanisms linking developmental phthalate exposures to long-term metabolic effects have not yet been elucidated. We investigated the hypothesis that developmental phthalate exposure has long-lasting impacts on PPAR target gene expression and DNA methylation to influence hepatic metabolic profiles across the life course. We utilized an established longitudinal mouse model of perinatal exposures to diethylhexyl phthalate and diisononyl phthalate, and a mixture of diethylhexyl phthalate+diisononyl phthalate. Exposure was through the diet and spanned from 2 weeks before mating until weaning at postnatal day 21 (PND21). Liver tissue was analyzed from the offspring of exposed and control mice at PND21 and in another cohort of exposed and control mice at 10 months of age. RNA-seq and pathway enrichment analyses indicated that acetyl-CoA metabolic processes were altered in diisononyl phthalate-exposed female livers at both PND21 and 10 months (FDR = 0.0018). Within the pathway, all 13 significant genes were potential PPAR target genes. Promoter DNA methylation was altered at three candidate genes, but persistent effects were only observed for <i>Fasn</i>. Targeted metabolomics indicated that phthalate-exposed females had decreased acetyl-CoA at PND21 and increased acetyl-CoA and acylcarnitines at 10 months. Together, our data suggested that perinatal phthalate exposures were associated with short- and long-term activation of PPAR target genes, which manifested as increased fatty acid production in early postnatal life and increased fatty acid oxidation in adulthood. This presents a novel molecular pathway linking developmental phthalate exposures and metabolic health outcomes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777160","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}
引用次数: 10
Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood. 母亲环境暴露于双酚类物质和婴儿脐带血表观基因组DNA甲基化。
IF 3.8 Q1 Environmental Science Pub Date : 2020-12-23 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa021
Carolyn F McCabe, Vasantha Padmanabhan, Dana C Dolinoy, Steven E Domino, Tamara R Jones, Kelly M Bakulski, Jaclyn M Goodrich

Maternal prenatal exposures, including bisphenol A (BPA), are associated with offspring's risk of disease later in life. Alterations in DNA methylation may be a mechanism through which altered prenatal conditions (e.g. maternal exposure to environmental toxicants) elicit this disease risk. In the Michigan Mother and Infant Pairs Cohort, maternal first-trimester urinary BPA, bisphenol F, and bisphenol S concentrations were tested for association with DNA methylation patterns in infant umbilical cord blood leukocytes (N = 69). We used the Illumina Infinium MethylationEPIC BeadChip to quantitatively evaluate DNA methylation across the epigenome; 822 020 probes passed pre-processing and quality checks. Single-site DNA methylation and bisphenol models were adjusted for infant sex, estimated cell-type proportions (determined using cell-type estimation algorithm), and batch as covariates. Thirty-eight CpG sites [false discovery rate (FDR) <0.05] were significantly associated with maternal BPA exposure. Increasing BPA concentrations were associated with lower DNA methylation at 87% of significant sites. BPA exposure associated DNA methylation sites were enriched for 38 pathways significant at FDR <0.05. The pathway or gene-set with the greatest odds of enrichment for differential methylation (FDR <0.05) was type I interferon receptor binding. This study provides a novel understanding of fetal response to maternal bisphenol exposure through epigenetic change.

母亲产前暴露,包括双酚A (BPA),与后代以后的疾病风险有关。DNA甲基化的改变可能是一种机制,通过这种机制,产前条件的改变(例如,母亲暴露于环境毒物)引发这种疾病风险。在密歇根母婴队列研究中,研究人员检测了孕妇妊娠早期尿液中BPA、双酚F和双酚S浓度与婴儿脐带血白细胞DNA甲基化模式的关系(N = 69)。我们使用Illumina Infinium MethylationEPIC珠片定量评估整个表观基因组的DNA甲基化;822020探针通过了预处理和质量检查。单位点DNA甲基化和双酚模型根据婴儿性别、估计的细胞类型比例(使用细胞类型估计算法确定)和批次作为协变量进行调整。38个CpG站点[错误发现率(FDR)]
{"title":"Maternal environmental exposure to bisphenols and epigenome-wide DNA methylation in infant cord blood.","authors":"Carolyn F McCabe,&nbsp;Vasantha Padmanabhan,&nbsp;Dana C Dolinoy,&nbsp;Steven E Domino,&nbsp;Tamara R Jones,&nbsp;Kelly M Bakulski,&nbsp;Jaclyn M Goodrich","doi":"10.1093/eep/dvaa021","DOIUrl":"https://doi.org/10.1093/eep/dvaa021","url":null,"abstract":"<p><p>Maternal prenatal exposures, including bisphenol A (BPA), are associated with offspring's risk of disease later in life. Alterations in DNA methylation may be a mechanism through which altered prenatal conditions (e.g. maternal exposure to environmental toxicants) elicit this disease risk. In the Michigan Mother and Infant Pairs Cohort, maternal first-trimester urinary BPA, bisphenol F, and bisphenol S concentrations were tested for association with DNA methylation patterns in infant umbilical cord blood leukocytes (<i>N</i> = 69). We used the Illumina Infinium MethylationEPIC BeadChip to quantitatively evaluate DNA methylation across the epigenome; 822 020 probes passed pre-processing and quality checks. Single-site DNA methylation and bisphenol models were adjusted for infant sex, estimated cell-type proportions (determined using cell-type estimation algorithm), and batch as covariates. Thirty-eight CpG sites [false discovery rate (FDR) <0.05] were significantly associated with maternal BPA exposure. Increasing BPA concentrations were associated with lower DNA methylation at 87% of significant sites. BPA exposure associated DNA methylation sites were enriched for 38 pathways significant at FDR <0.05. The pathway or gene-set with the greatest odds of enrichment for differential methylation (FDR <0.05) was type I interferon receptor binding. This study provides a novel understanding of fetal response to maternal bisphenol exposure through epigenetic change.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777164","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}
引用次数: 16
Epigenome-wide association study (EWAS) for potential transgenerational disease epigenetic biomarkers in sperm following ancestral exposure to the pesticide methoxychlor. 祖先接触杀虫剂甲氧氯后精子中潜在的跨代疾病表观遗传生物标志物的全基因组关联研究
IF 3.8 Q1 Environmental Science Pub Date : 2020-12-22 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa020
Eric E Nilsson, Jennifer L M Thorson, Millissia Ben Maamar, Daniel Beck, Michael K Skinner

Environmental exposures such as chemical toxicants can alter gene expression and disease susceptibility through epigenetic processes. Epigenetic changes can be passed to future generations through germ cells through epigenetic transgenerational inheritance of increased disease susceptibility. The current study used an epigenome-wide association study (EWAS) to investigate whether specific transgenerational epigenetic signatures of differential DNA methylation regions (DMRs) exist that are associated with particular disease states in the F3 generation great-grand offspring of F0 generation rats exposed during gestation to the agricultural pesticide methoxychlor. The transgenerational epigenetic profiles of sperm from F3 generation methoxychlor lineage rats that have only one disease state were compared to those that have no disease. Observations identify disease specific patterns of DMRs for these transgenerational rats that can potentially serve as epigenetic biomarkers for prostate disease, kidney disease, obesity, and the presence of multiple diseases. The chromosomal locations, genomic features, and gene associations of the DMRs are characterized. Disease specific DMR sets contained DMR-associated genes that have previously been shown to be associated with that specific disease. Future epigenetic biomarkers could potentially be developed and validated for humans as a disease susceptibility diagnostic tool to facilitate preventative medicine and management of disease.

环境暴露如化学毒物可以通过表观遗传过程改变基因表达和疾病易感性。表观遗传变化可以通过生殖细胞通过增加疾病易感性的表观遗传跨代遗传传递给后代。目前的研究使用全表观基因组关联研究(EWAS)来调查在妊娠期暴露于农药甲氧氯的F0代大鼠的F3代曾代后代中是否存在与特定疾病状态相关的差异DNA甲基化区域(DMRs)的特定跨代表观遗传特征。比较了F3代甲氧基氯系大鼠精子的跨代表观遗传特征,这些大鼠只有一种疾病状态和没有疾病状态。观察发现这些跨代大鼠的DMRs疾病特异性模式,可能作为前列腺疾病、肾脏疾病、肥胖和多种疾病存在的表观遗传生物标志物。染色体位置、基因组特征和DMRs的基因关联被表征。疾病特异性DMR组包含先前已被证明与该特定疾病相关的DMR相关基因。未来的表观遗传生物标志物有可能被开发和验证为人类疾病易感性诊断工具,以促进预防医学和疾病管理。
{"title":"Epigenome-wide association study (EWAS) for potential transgenerational disease epigenetic biomarkers in sperm following ancestral exposure to the pesticide methoxychlor.","authors":"Eric E Nilsson,&nbsp;Jennifer L M Thorson,&nbsp;Millissia Ben Maamar,&nbsp;Daniel Beck,&nbsp;Michael K Skinner","doi":"10.1093/eep/dvaa020","DOIUrl":"https://doi.org/10.1093/eep/dvaa020","url":null,"abstract":"<p><p>Environmental exposures such as chemical toxicants can alter gene expression and disease susceptibility through epigenetic processes. Epigenetic changes can be passed to future generations through germ cells through epigenetic transgenerational inheritance of increased disease susceptibility. The current study used an epigenome-wide association study (EWAS) to investigate whether specific transgenerational epigenetic signatures of differential DNA methylation regions (DMRs) exist that are associated with particular disease states in the F3 generation great-grand offspring of F0 generation rats exposed during gestation to the agricultural pesticide methoxychlor. The transgenerational epigenetic profiles of sperm from F3 generation methoxychlor lineage rats that have only one disease state were compared to those that have no disease. Observations identify disease specific patterns of DMRs for these transgenerational rats that can potentially serve as epigenetic biomarkers for prostate disease, kidney disease, obesity, and the presence of multiple diseases. The chromosomal locations, genomic features, and gene associations of the DMRs are characterized. Disease specific DMR sets contained DMR-associated genes that have previously been shown to be associated with that specific disease. Future epigenetic biomarkers could potentially be developed and validated for humans as a disease susceptibility diagnostic tool to facilitate preventative medicine and management of disease.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/83/dvaa020.PMC7757123.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38777161","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}
引用次数: 9
Prenatal lead exposure and cord blood DNA methylation in PROGRESS: an epigenome-wide association study. 产前铅暴露和脐带血DNA甲基化进展:一项全表观基因组关联研究。
IF 3.8 Q1 Environmental Science Pub Date : 2020-12-08 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa014
Jonathan A Heiss, Martha M Téllez-Rojo, Guadalupe Estrada-Gutiérrez, Lourdes Schnaas, Chitra Amarasiriwardena, Andrea A Baccarelli, Robert O Wright, Allan C Just

The effects of prenatal lead exposure on child development include impaired growth and cognitive function. DNA methylation might be involved in the underlying mechanisms and previous epigenome-wide association studies reported associations between lead exposure during pregnancy and cord blood methylation levels. However, it is unclear during which developmental stage lead exposure is most harmful. Cord blood methylation levels were assayed in 420 children from a Mexican pre-birth cohort using the Illumina Infinium MethylationEPIC microarray. Lead concentrations were measured in umbilical cord blood as well as in blood samples from the mothers collected at 2nd and 3rd trimester and delivery using inductively coupled plasma-mass spectrometry. In addition, maternal bone lead levels were measured in tibia and patella using X-ray fluorescence. Comprehensive quality control and preprocessing of microarray data was followed by an unbiased restriction to methylation sites with substantial variance. Methylation levels at 202 111 cytosine-phosphate-guanine sites were regressed on each exposure adjusting for child sex, leukocyte composition, batch variables, gestational age, birthweight-for-gestational-age, maternal age, maternal education and mode of delivery. We find no association between prenatal lead exposure and cord blood methylation. This null result is strengthened by a sensitivity analysis showing that in the same dataset known biomarkers for birthweight-for-gestational-age can be recovered and the fact that phenotypic associations with lead exposure have been described in the same cohort.

产前铅暴露对儿童发育的影响包括生长和认知功能受损。DNA甲基化可能涉及潜在的机制,之前的全表观基因组关联研究报告了妊娠期间铅暴露与脐带血甲基化水平之间的关联。然而,尚不清楚在哪个发育阶段铅暴露是最有害的。使用Illumina Infinium MethylationEPIC微阵列检测来自墨西哥产前队列的420名儿童的脐带血甲基化水平。使用电感耦合血浆质谱法测量脐带血中的铅浓度以及在妊娠第2和第3个月和分娩时收集的母亲的血液样本。此外,利用x射线荧光测定了产妇胫骨和髌骨的骨铅水平。对微阵列数据进行全面的质量控制和预处理,然后对存在较大差异的甲基化位点进行无偏限制。在每次暴露后,对202 - 111个胞嘧啶-磷酸-鸟嘌呤位点的甲基化水平进行回归,调整了儿童性别、白细胞组成、批次变量、胎龄、出生体重/胎龄、母亲年龄、母亲教育程度和分娩方式。我们没有发现产前铅暴露和脐带血甲基化之间的联系。敏感性分析表明,在同一数据集中可以恢复已知的出生体重与胎龄的生物标志物,并且在同一队列中描述了与铅暴露的表型关联,从而加强了这一无效结果。
{"title":"Prenatal lead exposure and cord blood DNA methylation in PROGRESS: an epigenome-wide association study.","authors":"Jonathan A Heiss,&nbsp;Martha M Téllez-Rojo,&nbsp;Guadalupe Estrada-Gutiérrez,&nbsp;Lourdes Schnaas,&nbsp;Chitra Amarasiriwardena,&nbsp;Andrea A Baccarelli,&nbsp;Robert O Wright,&nbsp;Allan C Just","doi":"10.1093/eep/dvaa014","DOIUrl":"https://doi.org/10.1093/eep/dvaa014","url":null,"abstract":"<p><p>The effects of prenatal lead exposure on child development include impaired growth and cognitive function. DNA methylation might be involved in the underlying mechanisms and previous epigenome-wide association studies reported associations between lead exposure during pregnancy and cord blood methylation levels. However, it is unclear during which developmental stage lead exposure is most harmful. Cord blood methylation levels were assayed in 420 children from a Mexican pre-birth cohort using the Illumina Infinium MethylationEPIC microarray. Lead concentrations were measured in umbilical cord blood as well as in blood samples from the mothers collected at 2nd and 3rd trimester and delivery using inductively coupled plasma-mass spectrometry. In addition, maternal bone lead levels were measured in tibia and patella using X-ray fluorescence. Comprehensive quality control and preprocessing of microarray data was followed by an unbiased restriction to methylation sites with substantial variance. Methylation levels at 202 111 cytosine-phosphate-guanine sites were regressed on each exposure adjusting for child sex, leukocyte composition, batch variables, gestational age, birthweight-for-gestational-age, maternal age, maternal education and mode of delivery. We find no association between prenatal lead exposure and cord blood methylation. This null result is strengthened by a sensitivity analysis showing that in the same dataset known biomarkers for birthweight-for-gestational-age can be recovered and the fact that phenotypic associations with lead exposure have been described in the same cohort.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716576","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}
引用次数: 8
Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health. 代谢性疾病影响雄性生殖,并在配子中诱发可能危及后代健康的特征。
IF 3.8 Q1 Environmental Science Pub Date : 2020-12-08 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa019
Sara C Pereira, Luís Crisóstomo, Mário Sousa, Pedro F Oliveira, Marco G Alves

The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with in vitro and animal models as well as in long-term transgenerational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the 'fat epidemic' efficiently.

世界上最普遍的疾病是非传染性的,如肥胖和2型糖尿病。值得注意的是,肥胖和2型糖尿病的患病率预计将在未来几十年稳步上升,主要是由于不良的饮食习惯、压力和久坐不动。个体的生殖功能受到异常代谢环境的严重影响,无论是在机械水平还是在生化水平。随着机械功能障碍和精子质量下降(由代谢异常直接或间接促进),一些研究已经报道了精子遗传和表观遗传货物中代谢障碍的潜在有害影响,以及代谢谱(父亲饮食、肥胖和糖尿病)诱导的分子特征的表观遗传。代谢异常发展的表观遗传因素的遗传意味着更多的育龄人群可能会遭受这些疾病的折磨,并且持续时间更长。反过来,这些个体也可以将这种遗传信息传递给后代,形成恶性循环。在这篇综述中,我们收集了有关获得性代谢紊乱和饮食对精子参数和男性生殖潜力的有害影响的报道。此外,我们还将讨论有关父亲表观遗传的新发现,特别是父亲高脂肪饮食、肥胖和2型糖尿病引起的表观遗传。我们分析了体外和动物模型以及长期跨代人口研究中获得的数据。虽然关于这一主题的发现是最近才发现的,但代谢性疾病的表观遗传具有巨大的社会影响,这可能是有效解决“肥胖流行病”的关键。
{"title":"Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health.","authors":"Sara C Pereira, Luís Crisóstomo, Mário Sousa, Pedro F Oliveira, Marco G Alves","doi":"10.1093/eep/dvaa019","DOIUrl":"10.1093/eep/dvaa019","url":null,"abstract":"<p><p>The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with <i>in vitro</i> and animal models as well as in long-term transgenerational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the 'fat epidemic' efficiently.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716581","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}
引用次数: 8
Differential susceptibility to endocrine disruptor-induced epimutagenesis. 对内分泌干扰物诱导的突变的不同易感性。
IF 4.8 Q1 GENETICS & HEREDITY Pub Date : 2020-12-08 eCollection Date: 2020-01-01 DOI: 10.1093/eep/dvaa016
Jake D Lehle, John R McCarrey

There is now considerable evidence indicating the potential for endocrine disrupting chemicals to alter the epigenome and for subsets of these epigenomic changes or "epimutations" to be heritably transmitted to offspring in subsequent generations. While there have been many studies indicating how exposure to endocrine disrupting chemicals can disrupt various organs associated with the body's endocrine systems, there is relatively limited information regarding the relative susceptibility of different specific organs, tissues, or cell types to endocrine disrupting chemical-induced epimutagenesis. Here we review available information about different organs, tissues, cell types, and/or cell lines which have been shown to be susceptible to specific endocrine disrupting chemical-induced epimutations. In addition, we discuss possible mechanisms that may be involved, or impacted by this tissue- or cell type-specific, differential susceptibility to different endocrine disrupting chemicals. Finally, we summarize available information indicating that certain periods of development display elevated susceptibility to endocrine disrupting chemical exposure and we describe how this may affect the extent to which germline epimutations can be transmitted inter- or transgenerationally. We conclude that cell type-specific differential susceptibility to endocrine disrupting chemical-induced epimutagenesis is likely to directly impact the extent to, or manner in, which endocrine disrupting chemical exposure initially induces epigenetic changes to DNA methylation and/or histone modifications, and how these endocrine disrupting chemical-induced epimutations can then subsequently impact gene expression, potentially leading to the development of heritable disease states.

现在有相当多的证据表明,内分泌干扰化学物质有可能改变表观基因组,这些表观基因组变化的子集或“表观突变”有可能遗传给后代。虽然有许多研究表明暴露于内分泌干扰化学物质如何破坏与人体内分泌系统相关的各种器官,但关于不同特定器官、组织或细胞类型对内分泌干扰化学物质诱导的表观突变的相对易感性的信息相对有限。在这里,我们回顾了关于不同器官、组织、细胞类型和/或细胞系的现有信息,这些信息已被证明对特定的内分泌干扰化学物质诱导的增殖敏感。此外,我们还讨论了可能涉及的机制,或受这种组织或细胞类型特异性,对不同内分泌干扰化学物质的差异易感性的影响。最后,我们总结了表明某些发育时期对内分泌干扰化学物质暴露的易感性升高的现有信息,并描述了这可能如何影响生殖系上皮细胞遗传在代际或跨代传播的程度。我们得出的结论是,细胞类型对内分泌干扰化学诱导的表观突变的特异性易感性可能直接影响内分泌干扰化学暴露最初诱导DNA甲基化和/或组蛋白修饰的表观遗传变化的程度或方式,以及这些内分泌干扰化学诱导的表观突变如何随后影响基因表达,从而可能导致遗传性疾病状态的发展。
{"title":"Differential susceptibility to endocrine disruptor-induced epimutagenesis.","authors":"Jake D Lehle, John R McCarrey","doi":"10.1093/eep/dvaa016","DOIUrl":"10.1093/eep/dvaa016","url":null,"abstract":"<p><p>There is now considerable evidence indicating the potential for endocrine disrupting chemicals to alter the epigenome and for subsets of these epigenomic changes or \"epimutations\" to be heritably transmitted to offspring in subsequent generations. While there have been many studies indicating how exposure to endocrine disrupting chemicals can disrupt various organs associated with the body's endocrine systems, there is relatively limited information regarding the relative susceptibility of different specific organs, tissues, or cell types to endocrine disrupting chemical-induced epimutagenesis. Here we review available information about different organs, tissues, cell types, and/or cell lines which have been shown to be susceptible to specific endocrine disrupting chemical-induced epimutations. In addition, we discuss possible mechanisms that may be involved, or impacted by this tissue- or cell type-specific, differential susceptibility to different endocrine disrupting chemicals. Finally, we summarize available information indicating that certain periods of development display elevated susceptibility to endocrine disrupting chemical exposure and we describe how this may affect the extent to which germline epimutations can be transmitted inter- or transgenerationally. We conclude that cell type-specific differential susceptibility to endocrine disrupting chemical-induced epimutagenesis is likely to directly impact the extent to, or manner in, which endocrine disrupting chemical exposure initially induces epigenetic changes to DNA methylation and/or histone modifications, and how these endocrine disrupting chemical-induced epimutations can then subsequently impact gene expression, potentially leading to the development of heritable disease states.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2020-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/03/dvaa016.PMC7722801.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38716578","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}
引用次数: 0
期刊
Environmental Epigenetics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1