首页 > 最新文献

Environmental Epigenetics最新文献

英文 中文
Developmental exposure to methylmercury and ADHD, a literature review of epigenetic studies. 发育暴露于甲基汞和多动症,表观遗传学研究的文献综述。
IF 3.8 Q1 Environmental Science Pub Date : 2021-11-22 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab014
Tao Ke, Alexey A Tinkov, Antoly V Skalny, Aaron B Bowman, Joao B T Rocha, Abel Santamaria, Michael Aschner

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects the competence of academic performance and social wellness in children and adults. The causes of ADHD are unclear. Both genetic and environmental factors contribute to the development of ADHD. The behavioral impairments in ADHD are associated with epigenetic changes in genes that are important for neurodevelopment. Among environmental causes of ADHD, the neurotoxin methylmercury (MeHg) is associated with an increased risk for ADHD. Developing children are susceptible to neurotoxic effects of prenatal MeHg exposure. Human epidemiology studies have shown that prenatal MeHg exposure could invoke epigenetic changes in genes that are involved in ADHD. In addition, the pathogenesis of ADHD involves dopaminergic system, which is a target of developmental MeHg exposure. MeHg-induced alterations in the dopaminergic system have a profound impact on behavioral functions in adults. As a trace level of MeHg (around nM) can induce long-lasting behavioral alterations, potential mechanisms of MeHg-induced functional changes in the dopaminergic system may involve epigenetic mechanisms. Here, we review the relevant evidence on developmental MeHg exposures and the risk for ADHD. We also point out research gaps in understanding environmental causes of ADHD.

注意缺陷多动障碍(ADHD)是一种影响儿童和成人学习能力和社会健康的神经发育障碍。ADHD的病因尚不清楚。遗传和环境因素都对多动症的发展有影响。多动症的行为障碍与对神经发育很重要的基因的表观遗传变化有关。在ADHD的环境因素中,神经毒素甲基汞(MeHg)与ADHD风险增加有关。发育中的儿童易受产前甲基汞暴露的神经毒性影响。人类流行病学研究表明,产前甲基汞暴露可能引发与多动症有关的基因的表观遗传变化。此外,ADHD的发病机制涉及多巴胺能系统,该系统是发育性甲基汞暴露的靶点。脑电诱导的多巴胺能系统的改变对成人的行为功能有深远的影响。微量甲基汞(nM左右)可引起长期的行为改变,甲基汞诱导多巴胺能系统功能改变的潜在机制可能涉及表观遗传机制。在此,我们回顾了发育性甲基汞暴露与ADHD风险的相关证据。我们还指出了在理解ADHD的环境原因方面的研究差距。
{"title":"Developmental exposure to methylmercury and ADHD, a literature review of epigenetic studies.","authors":"Tao Ke,&nbsp;Alexey A Tinkov,&nbsp;Antoly V Skalny,&nbsp;Aaron B Bowman,&nbsp;Joao B T Rocha,&nbsp;Abel Santamaria,&nbsp;Michael Aschner","doi":"10.1093/eep/dvab014","DOIUrl":"https://doi.org/10.1093/eep/dvab014","url":null,"abstract":"<p><p>Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects the competence of academic performance and social wellness in children and adults. The causes of ADHD are unclear. Both genetic and environmental factors contribute to the development of ADHD. The behavioral impairments in ADHD are associated with epigenetic changes in genes that are important for neurodevelopment. Among environmental causes of ADHD, the neurotoxin methylmercury (MeHg) is associated with an increased risk for ADHD. Developing children are susceptible to neurotoxic effects of prenatal MeHg exposure. Human epidemiology studies have shown that prenatal MeHg exposure could invoke epigenetic changes in genes that are involved in ADHD. In addition, the pathogenesis of ADHD involves dopaminergic system, which is a target of developmental MeHg exposure. MeHg-induced alterations in the dopaminergic system have a profound impact on behavioral functions in adults. As a trace level of MeHg (around nM) can induce long-lasting behavioral alterations, potential mechanisms of MeHg-induced functional changes in the dopaminergic system may involve epigenetic mechanisms. Here, we review the relevant evidence on developmental MeHg exposures and the risk for ADHD. We also point out research gaps in understanding environmental causes of ADHD.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39817100","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
Role of environmentally induced epigenetic transgenerational inheritance in evolutionary biology: Unified Evolution Theory. 环境诱导的表观遗传跨代遗传在进化生物学中的作用:统一进化理论。
IF 3.8 Q1 Environmental Science Pub Date : 2021-10-30 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab012
Michael K Skinner, Eric E Nilsson

The current evolutionary biology theory primarily involves genetic alterations and random DNA sequence mutations to generate the phenotypic variation required for Darwinian natural selection to act. This neo-Darwinian evolution is termed the Modern Evolution Synthesis and has been the primary paradigm for nearly 100 years. Although environmental factors have a role in neo-Darwinian natural selection, Modern Evolution Synthesis does not consider environment to impact the basic molecular processes involved in evolution. An Extended Evolutionary Synthesis has recently developed that extends the modern synthesis to consider non-genetic processes. Over the past few decades, environmental epigenetics research has been demonstrated to regulate genetic processes and directly generate phenotypic variation independent of genetic sequence alterations. Therefore, the environment can on a molecular level through non-genetic (i.e. epigenetic) mechanisms directly influence phenotypic variation, genetic variation, inheritance and adaptation. This direct action of the environment to alter phenotype that is heritable is a neo-Lamarckian concept that can facilitate neo-Darwinian (i.e. Modern Synthesis) evolution. The integration of genetics, epigenetics, Darwinian theory, Lamarckian concepts, environment, and epigenetic inheritance provides a paradigm shift in evolution theory. The role of environmental-induced epigenetic transgenerational inheritance in evolution is presented to describe a more unified theory of evolutionary biology.

目前的进化生物学理论主要涉及基因改变和随机DNA序列突变,以产生达尔文自然选择所需的表型变异。这种新达尔文进化被称为现代进化综合,近100年来一直是主要的范式。虽然环境因素在新达尔文的自然选择中发挥了作用,但现代进化综合理论并未考虑环境对进化中涉及的基本分子过程的影响。最近发展了一种扩展进化综合,将现代综合扩展到考虑非遗传过程。在过去的几十年里,环境表观遗传学研究已经被证明可以调节遗传过程并直接产生不依赖于基因序列改变的表型变异。因此,环境可以在分子水平上通过非遗传(即表观遗传)机制直接影响表型变异、遗传变异、遗传和适应。这种环境改变可遗传表型的直接作用是新拉马克的概念,可以促进新达尔文(即现代综合)进化。遗传学、表观遗传学、达尔文理论、拉马克概念、环境和表观遗传的整合提供了进化理论的范式转变。环境诱导的表观遗传跨代遗传在进化中的作用是为了描述一个更统一的进化生物学理论。
{"title":"Role of environmentally induced epigenetic transgenerational inheritance in evolutionary biology: Unified Evolution Theory.","authors":"Michael K Skinner,&nbsp;Eric E Nilsson","doi":"10.1093/eep/dvab012","DOIUrl":"https://doi.org/10.1093/eep/dvab012","url":null,"abstract":"<p><p>The current evolutionary biology theory primarily involves genetic alterations and random DNA sequence mutations to generate the phenotypic variation required for Darwinian natural selection to act. This neo-Darwinian evolution is termed the Modern Evolution Synthesis and has been the primary paradigm for nearly 100 years. Although environmental factors have a role in neo-Darwinian natural selection, Modern Evolution Synthesis does not consider environment to impact the basic molecular processes involved in evolution. An Extended Evolutionary Synthesis has recently developed that extends the modern synthesis to consider non-genetic processes. Over the past few decades, environmental epigenetics research has been demonstrated to regulate genetic processes and directly generate phenotypic variation independent of genetic sequence alterations. Therefore, the environment can on a molecular level through non-genetic (i.e. epigenetic) mechanisms directly influence phenotypic variation, genetic variation, inheritance and adaptation. This direct action of the environment to alter phenotype that is heritable is a neo-Lamarckian concept that can facilitate neo-Darwinian (i.e. Modern Synthesis) evolution. The integration of genetics, epigenetics, Darwinian theory, Lamarckian concepts, environment, and epigenetic inheritance provides a paradigm shift in evolution theory. The role of environmental-induced epigenetic transgenerational inheritance in evolution is presented to describe a more unified theory of evolutionary biology.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/9a/dvab012.PMC8557805.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39689907","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: 31
Prenatal exposure to a mixture of phthalates accelerates the age-related decline in reproductive capacity but may not affect direct biomarkers of ovarian aging in the F1 generation of female mice. 产前接触邻苯二甲酸盐混合物会加速生殖能力与年龄相关的下降,但可能不会影响 F1 代雌性小鼠卵巢衰老的直接生物标志物。
IF 3.8 Q1 Environmental Science Pub Date : 2021-10-25 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab010
Emily Brehm, Jodi A Flaws

Phthalates are used in many consumer products, leading to daily human exposure. Although many studies focus on single phthalates, humans are exposed to mixtures of phthalates. Our laboratory created a phthalate mixture consisting of six different phthalates and found that it negatively affected female reproduction and accelerated some biomarkers of reproductive aging. However, it was unknown if prenatal exposure to the mixture accelerates the natural decline in reproductive capacity and ovarian aging in mice. Therefore, we tested the hypothesis that prenatal exposure to a phthalate mixture accelerates the age-related decline in reproductive capacity and biomarkers of ovarian aging in the F1 generation of mice. Pregnant CD-1 dams were orally dosed with control or phthalate mixture (20 µg/kg/day-200 mg/kg/day) daily from gestational day 10-birth. The F1 female pups were aged to 11-13 months, and then estrous cyclicity and breeding trials were conducted at 11 and 13 months. Ovaries were collected from the F1 females at 13 months to examine biomarkers of ovarian aging. Prenatal exposure to the phthalate mixture decreased the time the F1 females spent in proestrus and the ability of the F1 females to give birth at 11 and 13 months of age compared to control. In contrast, prenatal exposure to the mixture did not affect biomarkers of direct aging of the ovary in the F1 generation. Collectively, our data show that prenatal phthalate mixture exposure accelerates the natural age-related decline in reproductive capacity but may not affect some biomarkers of ovarian aging in the F1 generation.

邻苯二甲酸盐被用于许多消费品中,导致人类每天都会接触到邻苯二甲酸盐。尽管许多研究侧重于单一的邻苯二甲酸盐,但人类也会接触到邻苯二甲酸盐混合物。我们的实验室创造了一种由六种不同邻苯二甲酸盐组成的邻苯二甲酸盐混合物,并发现它对女性生殖产生了负面影响,并加速了生殖衰老的一些生物标志物。然而,产前暴露于这种混合物是否会加速小鼠生殖能力的自然衰退和卵巢衰老尚不清楚。因此,我们测试了产前接触邻苯二甲酸酯混合物会加速 F1 代小鼠生殖能力和卵巢衰老生物标志物与年龄相关的衰退这一假设。怀孕的 CD-1 母鼠从妊娠第 10 天-出生后每天口服对照组或邻苯二甲酸酯混合物(20 微克/千克/天-200 毫克/千克/天)。F1雌性幼崽长到11-13个月大,然后在11和13个月大时进行发情周期和繁殖试验。在 F1 雌性幼鼠 13 个月时收集其卵巢,以检测卵巢衰老的生物标志物。与对照组相比,产前暴露于邻苯二甲酸盐混合物会减少 F1 雌性发情的时间,并降低 F1 雌性在 11 和 13 个月大时的生育能力。相比之下,产前接触该混合物并不会影响 F1 代卵巢直接衰老的生物标志物。总之,我们的数据表明,产前接触邻苯二甲酸酯混合物会加速生殖能力与年龄相关的自然衰退,但可能不会影响 F1 代卵巢衰老的一些生物标志物。
{"title":"Prenatal exposure to a mixture of phthalates accelerates the age-related decline in reproductive capacity but may not affect direct biomarkers of ovarian aging in the F1 generation of female mice.","authors":"Emily Brehm, Jodi A Flaws","doi":"10.1093/eep/dvab010","DOIUrl":"10.1093/eep/dvab010","url":null,"abstract":"<p><p>Phthalates are used in many consumer products, leading to daily human exposure. Although many studies focus on single phthalates, humans are exposed to mixtures of phthalates. Our laboratory created a phthalate mixture consisting of six different phthalates and found that it negatively affected female reproduction and accelerated some biomarkers of reproductive aging. However, it was unknown if prenatal exposure to the mixture accelerates the natural decline in reproductive capacity and ovarian aging in mice. Therefore, we tested the hypothesis that prenatal exposure to a phthalate mixture accelerates the age-related decline in reproductive capacity and biomarkers of ovarian aging in the F1 generation of mice. Pregnant CD-1 dams were orally dosed with control or phthalate mixture (20 µg/kg/day-200 mg/kg/day) daily from gestational day 10-birth. The F1 female pups were aged to 11-13 months, and then estrous cyclicity and breeding trials were conducted at 11 and 13 months. Ovaries were collected from the F1 females at 13 months to examine biomarkers of ovarian aging. Prenatal exposure to the phthalate mixture decreased the time the F1 females spent in proestrus and the ability of the F1 females to give birth at 11 and 13 months of age compared to control. In contrast, prenatal exposure to the mixture did not affect biomarkers of direct aging of the ovary in the F1 generation. Collectively, our data show that prenatal phthalate mixture exposure accelerates the natural age-related decline in reproductive capacity but may not affect some biomarkers of ovarian aging in the F1 generation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/fd/dvab010.PMC8543146.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39564274","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
DNA methylation changes induced by prenatal toxic metal exposure: An overview of epidemiological evidence. 产前有毒金属暴露引起的DNA甲基化变化:流行病学证据综述。
IF 3.8 Q1 Environmental Science Pub Date : 2021-10-06 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab007
Alexander Vaiserman, Oleh Lushchak

Accumulating evidence suggests that exposure to unfavorable conditions early in life can substantially contribute to the risk of chronic disorders later in life ('developmental programming' phenomenon). The mechanistic basis for this phenomenon remains poorly understood so far, although epigenetic mechanisms such as DNA methylation, histone modifications and microRNA-mediated gene regulation apparently play a crucial role. The key role of epigenetic modifications triggered by unfavorable environmental cues during sensitive developmental periods in linking adverse early-life events to later-life health outcomes is evident from a large body of studies, including methylome-wide association studies and research of candidate genes. Toxic metals (TMs), such as heavy metals, including lead, chromium, cadmium, arsenic, mercury, etc., are among environmental contaminants currently most significantly impacting human health status. Since TMs can cross the placental barrier and accumulate in fetal tissues, exposure to high doses of these xenobiotics early in development is considered to be among important factors contributing to the developmental programming of adult-life diseases in modern societies. In this mini-review, we summarize epidemiological findings indicating that prenatal TM exposure can induce epigenetic dysregulation, thereby potentially affecting adult health outcomes.

越来越多的证据表明,生命早期暴露于不利的环境会大大增加生命后期患慢性疾病的风险(“发育规划”现象)。尽管表观遗传机制,如DNA甲基化、组蛋白修饰和microrna介导的基因调控显然起着至关重要的作用,但迄今为止,这种现象的机制基础仍然知之甚少。大量研究表明,在敏感的发育时期,由不利的环境因素引发的表观遗传修饰在将不良的早期生活事件与晚年健康结果联系起来方面发挥着关键作用,包括甲基组全关联研究和候选基因研究。有毒金属(TMs),如重金属,包括铅、铬、镉、砷、汞等,是目前影响人类健康状况最严重的环境污染物之一。由于TMs可以穿过胎盘屏障并在胎儿组织中积累,因此在发育早期暴露于高剂量这些外源药物被认为是导致现代社会成年期疾病发展规划的重要因素之一。在这篇小型综述中,我们总结了流行病学研究结果,表明产前TM暴露可诱导表观遗传失调,从而可能影响成人的健康结果。
{"title":"DNA methylation changes induced by prenatal toxic metal exposure: An overview of epidemiological evidence.","authors":"Alexander Vaiserman,&nbsp;Oleh Lushchak","doi":"10.1093/eep/dvab007","DOIUrl":"https://doi.org/10.1093/eep/dvab007","url":null,"abstract":"<p><p>Accumulating evidence suggests that exposure to unfavorable conditions early in life can substantially contribute to the risk of chronic disorders later in life ('developmental programming' phenomenon). The mechanistic basis for this phenomenon remains poorly understood so far, although epigenetic mechanisms such as DNA methylation, histone modifications and microRNA-mediated gene regulation apparently play a crucial role. The key role of epigenetic modifications triggered by unfavorable environmental cues during sensitive developmental periods in linking adverse early-life events to later-life health outcomes is evident from a large body of studies, including methylome-wide association studies and research of candidate genes. Toxic metals (TMs), such as heavy metals, including lead, chromium, cadmium, arsenic, mercury, etc., are among environmental contaminants currently most significantly impacting human health status. Since TMs can cross the placental barrier and accumulate in fetal tissues, exposure to high doses of these xenobiotics early in development is considered to be among important factors contributing to the developmental programming of adult-life diseases in modern societies. In this mini-review, we summarize epidemiological findings indicating that prenatal TM exposure can induce epigenetic dysregulation, thereby potentially affecting adult health outcomes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/cc/dvab007.PMC8493661.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39505622","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: 6
Refraining from use diminishes cannabis-associated epigenetic changes in human sperm. 不使用大麻会减少人类精子中与大麻相关的表观遗传变化。
IF 3.8 Q1 Environmental Science Pub Date : 2021-09-21 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab009
Rose Schrott, Susan K Murphy, Jennifer L Modliszewski, Dillon E King, Bendu Hill, Nilda Itchon-Ramos, Douglas Raburn, Thomas Price, Edward D Levin, Ryan Vandrey, David L Corcoran, Scott H Kollins, John T Mitchell

Cannabis use alters sperm DNA methylation, but the potential reversibility of these changes is unknown. Semen samples from cannabis users and non-user controls were collected at baseline and again following a 77-day period of cannabis abstinence (one spermatogenic cycle). Users and controls did not significantly differ by demographics or semen analyses. Whole-genome bisulfite sequencing identified 163 CpG sites with significantly different DNA methylation in sperm between groups (P < 2.94 × 10-9). Genes associated with altered CpG sites were enriched with those involved in development, including cardiogenesis and neurodevelopment. Many of the differences in sperm DNA methylation between groups were diminished after cannabis abstinence. These results indicate that sustained cannabis abstinence significantly reduces the number of sperm showing cannabis-associated alterations at genes important for early development.

使用大麻会改变精子DNA甲基化,但这些变化的潜在可逆性尚不清楚。在基线时收集大麻使用者和非使用者对照的精液样本,并在77天的大麻戒断期(一个生精周期)后再次收集。使用者和对照组在人口统计学或精液分析方面没有显著差异。亚硫酸氢盐全基因组测序鉴定出163个CpG位点在两组精子中DNA甲基化有显著差异(P -9)。与CpG位点改变相关的基因与发育相关的基因丰富,包括心脏发生和神经发育。在戒掉大麻后,两组之间精子DNA甲基化的许多差异都消失了。这些结果表明,持续的大麻戒断显着减少精子的数量,显示大麻相关的基因改变对早期发育很重要。
{"title":"Refraining from use diminishes cannabis-associated epigenetic changes in human sperm.","authors":"Rose Schrott,&nbsp;Susan K Murphy,&nbsp;Jennifer L Modliszewski,&nbsp;Dillon E King,&nbsp;Bendu Hill,&nbsp;Nilda Itchon-Ramos,&nbsp;Douglas Raburn,&nbsp;Thomas Price,&nbsp;Edward D Levin,&nbsp;Ryan Vandrey,&nbsp;David L Corcoran,&nbsp;Scott H Kollins,&nbsp;John T Mitchell","doi":"10.1093/eep/dvab009","DOIUrl":"https://doi.org/10.1093/eep/dvab009","url":null,"abstract":"<p><p>Cannabis use alters sperm DNA methylation, but the potential reversibility of these changes is unknown. Semen samples from cannabis users and non-user controls were collected at baseline and again following a 77-day period of cannabis abstinence (one spermatogenic cycle). Users and controls did not significantly differ by demographics or semen analyses. Whole-genome bisulfite sequencing identified 163 CpG sites with significantly different DNA methylation in sperm between groups (<i>P</i> < 2.94 × 10<sup>-9</sup>). Genes associated with altered CpG sites were enriched with those involved in development, including cardiogenesis and neurodevelopment. Many of the differences in sperm DNA methylation between groups were diminished after cannabis abstinence. These results indicate that sustained cannabis abstinence significantly reduces the number of sperm showing cannabis-associated alterations at genes important for early development.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/64/20/dvab009.PMC8455898.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39444072","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: 35
Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver. 多氯联苯和高脂肪饮食的联合暴露改变了小鼠肝脏的整体表转录组学景观。
IF 3.8 Q1 Environmental Science Pub Date : 2021-09-17 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab008
Carolyn M Klinge, Kellianne M Piell, Belinda J Petri, Liqing He, Xiang Zhang, Jianmin Pan, Shesh N Rai, Kalina Andreeva, Eric C Rouchka, Banrida Wahlang, Juliane I Beier, Matthew C Cave

Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.

暴露于单剂量多氯联苯(PCBs)和12周高脂肪饮食(HFD)会通过改变细胞内信号传导和抑制表皮生长因子受体信号传导导致小鼠非酒精性脂肪性肝炎(NASH)。RNA的转录后化学修饰(PTM)调节生物过程,但表观转录组学对多氯联苯诱导的脂肪变性的贡献尚不清楚。本研究验证了PCB和HFD暴露改变雄性小鼠肝脏整体RNA表转录组的假设。C57BL/6J雄性小鼠连续喂食HFD 12周,在连续喂食HFD 2周后,分别给予单剂量Aroclor 1260 (20 mg/kg)、PCB 126(20µg/kg)、Aroclor 1260和PCB 126或对照。采用液相色谱-质谱联用技术在核苷水平鉴定了化学RNA修饰。从22个PTM全局RNA修饰中,我们确定了HFD和PCB 126暴露后肝脏中RNA修饰的10个显著变化。在所有三个PCB暴露组中,只有两种修饰与HFD对照肝有显著差异:2'- o -甲基腺苷(Am)和N(6)-甲基腺苷(m6A)。暴露于HFD + PCB 126 + Aroclor 1260增加了N(6), O(2)-二甲基腺苷(m6Am)的丰度,这与转录物变化的数量最多有关。在HFD + PCB 126- + Aroclor 1260暴露的小鼠肝脏中,m6Am和伪尿嘧啶的增加分别与磷酸化CTD相互作用因子1 (PCIF1)和伪尿嘧啶合成酶10 (PUS10)的蛋白表达增加有关。增加的n1 -甲基腺苷(m1A)和m6A与这些修饰的读取器的转录水平增加有关:YTH n6 -甲基腺苷RNA结合蛋白2 (YTHDF2), YTH结构域2 (YTHDC2),以及读取器FMRP翻译调节因子1 (FMR1)转录物和蛋白质丰度。结果表明,PCB暴露改变了NASH小鼠模型的全局表转录组;然而,这些变化的机制需要进一步研究。
{"title":"Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.","authors":"Carolyn M Klinge, Kellianne M Piell, Belinda J Petri, Liqing He, Xiang Zhang, Jianmin Pan, Shesh N Rai, Kalina Andreeva, Eric C Rouchka, Banrida Wahlang, Juliane I Beier, Matthew C Cave","doi":"10.1093/eep/dvab008","DOIUrl":"10.1093/eep/dvab008","url":null,"abstract":"<p><p>Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731720","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
Corrigendum to: Adolescent Epigenetic Profiles and Environmental Exposures from Early Life through Peri-Adolescence. 青少年表观遗传特征和从生命早期到青春期周围的环境暴露的勘误。
IF 3.8 Q1 Environmental Science Pub Date : 2021-08-11 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab006

[This corrects the article DOI: 10.1093/eep/dvw018.].

[这更正了文章DOI: 10.1093/eep/dvw018.]。
{"title":"Corrigendum to: Adolescent Epigenetic Profiles and Environmental Exposures from Early Life through Peri-Adolescence.","authors":"","doi":"10.1093/eep/dvab006","DOIUrl":"https://doi.org/10.1093/eep/dvab006","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/eep/dvw018.].</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/61/dvab006.PMC8496744.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39505621","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
DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes. 出生时的 DNA 甲基化可能会介导产前铅(Pb)暴露与婴儿神经发育结果之间的关系。
IF 4.8 Q1 GENETICS & HEREDITY Pub Date : 2021-06-16 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab005
Christine A Rygiel, Dana C Dolinoy, Kelly M Bakulski, Max T Aung, Wei Perng, Tamara R Jones, Maritsa Solano-González, Howard Hu, Martha M Tellez-Rojo, Lourdes Schnaas, Erika Marcela, Karen E Peterson, Jaclyn M Goodrich

Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), P = 0.06] and emotional regulation [3.62 (-0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), P = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.

早年的铅(Pb)暴露与不良的神经发育结果有关。最近的证据表明,DNA 甲基化(DNAm)在认知中起着关键作用,而铅暴露也被证明会改变 DNAm。然而,DNAm是否是铅神经毒性机制的一部分尚不清楚。这项纵向研究调查了墨西哥早期环境毒物暴露(ELEMENT)研究中 85 对母婴的特定孕期(T1、T2 和 T3)母体血液中铅浓度、脐带血中基因特异性 DNAm 与婴儿 12 个月和 24 个月大时神经发育结果(智力发育指数、精神运动发育指数以及定向/参与和情绪调节行为评分量表)之间的关系。在这项试点研究的中介分析中,P CCSER1(探针 ID cg02901723)中介了 T2 Pb 对 24 个月定向/参与的影响[间接效应估计值 4.44,95% 置信区间 (-0.09, 10.68),P = 0.06]和情绪调节[3.62 (-0.05, 8.69),P = 0.05]。Cg18515027(GCNT1)DNAm介导了T1 Pb [-4.94 (-10.6, -0.77),P = 0.01]和T2 Pb [-3.52 (-8.09, -0.36),P = 0.02]与24个月EMOCI的关联,但T2 Pb与24个月精神运动发育指数之间存在正的间接效应估计值[1.25 (-0.11, 3.32),P = 0.09]。cg19703494(TRAPPC6A)DNAm的间接效应在T2 Pb与24个月精神发育指数之间具有显著性[1.54(0,3.87),P = 0.05]。cg23280166 (VPS11) DNAm 对 T3 Pb 和 24 个月智力发育指数也有间接影响 [2.43 (-0.16, 6.38),P = 0.08]。这些关联提供了基因特异性 DNAm 作为产前铅与后代不良认知结果之间中介的初步证据。
{"title":"DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes.","authors":"Christine A Rygiel, Dana C Dolinoy, Kelly M Bakulski, Max T Aung, Wei Perng, Tamara R Jones, Maritsa Solano-González, Howard Hu, Martha M Tellez-Rojo, Lourdes Schnaas, Erika Marcela, Karen E Peterson, Jaclyn M Goodrich","doi":"10.1093/eep/dvab005","DOIUrl":"10.1093/eep/dvab005","url":null,"abstract":"<p><p>Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, <i>P</i> < 0.1 was considered significant. DNAm at a locus in <i>CCSER1</i> (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), <i>P</i> = 0.06] and emotional regulation [3.62 (-0.05, 8.69), <i>P</i> = 0.05]. Cg18515027 (<i>GCNT1</i>) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), <i>P</i> = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), <i>P</i> = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), <i>P</i> = 0.09]. The indirect effect was significant for cg19703494 (<i>TRAPPC6A</i>) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), <i>P</i> = 0.05]. There was also an indirect effect of cg23280166 (<i>VPS11</i>) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), <i>P</i> = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2021-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/35/dvab005.PMC8206046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177640","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
Differential DNA methylation in somatic and sperm cells of hatchery vs wild (natural-origin) steelhead trout populations. 孵化场与野生(天然)虹鳟种群的体细胞和精子细胞DNA甲基化差异。
IF 3.8 Q1 Environmental Science Pub Date : 2021-05-19 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab002
Eric Nilsson, Ingrid Sadler-Riggleman, Daniel Beck, Michael K Skinner

Environmental factors such as nutrition, stress, and toxicants can influence epigenetic programming and phenotypes of a wide variety of species from plants to humans. The current study was designed to investigate the impacts of hatchery spawning and rearing on steelhead trout (Oncorhynchus mykiss) vs the wild fish on a molecular level. Additionally, epigenetic differences between feeding practices that allow slow growth (2 years) and fast growth (1 year) hatchery trout were investigated. The sperm and red blood cells (RBC) from adult male slow growth/maturation hatchery steelhead, fast growth/maturation hatchery steelhead, and wild (natural-origin) steelhead were collected for DNA preparation to investigate potential alterations in differential DNA methylation regions (DMRs) and genetic mutations, involving copy number variations (CNVs). The sperm and RBC DNA both had a large number of DMRs when comparing the hatchery vs wild steelhead trout populations. The DMRs were cell type specific with negligible overlap. Slow growth/maturation compared to fast growth/maturation steelhead also had a larger number of DMRs in the RBC samples. A number of the DMRs had associated genes that were correlated to various biological processes and pathologies. Observations demonstrate a major epigenetic programming difference between the hatchery and wild natural-origin fish populations, but negligible genetic differences. Therefore, hatchery conditions and growth/maturation rate can alter the epigenetic developmental programming of the steelhead trout. Interestingly, epigenetic alterations in the sperm allow for potential epigenetic transgenerational inheritance of phenotypic variation to future generations. The impacts of hatchery exposures are not only important to consider on the fish exposed, but also on future generations and evolutionary trajectory of fish in the river populations.

环境因素,如营养、压力和毒物可以影响从植物到人类的各种物种的表观遗传程序和表型。本研究旨在探讨在分子水平上孵育、产卵和饲养对虹鳟和野生虹鳟的影响。此外,还研究了慢生长(2年)和快生长(1年)孵化场鳟鱼饲养方式之间的表观遗传差异。收集成年雄性慢生长/成熟孵化场钢头、快速生长/成熟孵化场钢头和野生(天然)钢头的精子和红细胞(RBC)进行DNA制备,研究差异DNA甲基化区(DMRs)和基因突变的潜在变化,包括拷贝数变异(CNVs)。在比较孵化场和野生虹鳟种群时,精子和红细胞DNA都有大量的DMRs。DMRs是细胞类型特异性的,重叠可以忽略不计。与快速生长/成熟的钢头鱼相比,缓慢生长/成熟的钢头鱼在RBC样本中也有更多的DMRs。许多dmr具有与各种生物过程和病理相关的相关基因。观察结果表明,在孵化场和野生天然鱼类种群之间存在主要的表观遗传编程差异,但遗传差异可以忽略不计。因此,孵卵条件和生长/成熟速率可以改变虹鳟的表观遗传发育程序。有趣的是,精子中的表观遗传改变允许表型变异的潜在表观遗传跨代遗传给后代。孵化场暴露不仅对暴露的鱼类有重要的影响,而且对河流种群中鱼类的后代和进化轨迹也有重要的影响。
{"title":"Differential DNA methylation in somatic and sperm cells of hatchery vs wild (natural-origin) steelhead trout populations.","authors":"Eric Nilsson,&nbsp;Ingrid Sadler-Riggleman,&nbsp;Daniel Beck,&nbsp;Michael K Skinner","doi":"10.1093/eep/dvab002","DOIUrl":"https://doi.org/10.1093/eep/dvab002","url":null,"abstract":"<p><p>Environmental factors such as nutrition, stress, and toxicants can influence epigenetic programming and phenotypes of a wide variety of species from plants to humans. The current study was designed to investigate the impacts of hatchery spawning and rearing on steelhead trout (<i>Oncorhynchus mykiss</i>) vs the wild fish on a molecular level. Additionally, epigenetic differences between feeding practices that allow slow growth (2 years) and fast growth (1 year) hatchery trout were investigated. The sperm and red blood cells (RBC) from adult male slow growth/maturation hatchery steelhead, fast growth/maturation hatchery steelhead, and wild (natural-origin) steelhead were collected for DNA preparation to investigate potential alterations in differential DNA methylation regions (DMRs) and genetic mutations, involving copy number variations (CNVs). The sperm and RBC DNA both had a large number of DMRs when comparing the hatchery vs wild steelhead trout populations. The DMRs were cell type specific with negligible overlap. Slow growth/maturation compared to fast growth/maturation steelhead also had a larger number of DMRs in the RBC samples. A number of the DMRs had associated genes that were correlated to various biological processes and pathologies. Observations demonstrate a major epigenetic programming difference between the hatchery and wild natural-origin fish populations, but negligible genetic differences. Therefore, hatchery conditions and growth/maturation rate can alter the epigenetic developmental programming of the steelhead trout. Interestingly, epigenetic alterations in the sperm allow for potential epigenetic transgenerational inheritance of phenotypic variation to future generations. The impacts of hatchery exposures are not only important to consider on the fish exposed, but also on future generations and evolutionary trajectory of fish in the river populations.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2021-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvab002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38940899","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: 6
Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells. 受控人类暴露于柴油废气:靶支气管上皮细胞的全人类表观基因组实验。
IF 4.8 Q1 GENETICS & HEREDITY Pub Date : 2021-04-09 eCollection Date: 2021-01-01 DOI: 10.1093/eep/dvab003
Andres Cardenas, Raj P Fadadu, Lars Van Der Laan, Cavin Ward-Caviness, Louis Granger, David Diaz-Sanchez, Robert B Devlin, Marie-Abèle Bind

Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact P-value of P =2.44 × 10-4 (i.e. 2/213). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (C5orf63; 7-CpGs) and unc-45 myosin chaperone A gene (UNC45A; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.

柴油废气(DE)是造成世界各地环境空气污染的主要因素。它是一种已知的人类致癌物,靶向呼吸系统,增加患许多疾病的风险,但关于DE暴露对人类支气管上皮细胞表观基因组的影响的研究有限。了解这种环境污染物的表观遗传学影响可以阐明与DE相关的有害健康影响的发病机制有关的生物学机制。为了估计短期DE暴露对支气管上皮表观基因组的因果影响,我们进行了一项DE暴露的对照单盲随机交叉人体实验,并分别使用支气管镜检查和Illumina 450K阵列进行数据收集和分析。在13名参与者中,11名(85%)为男性,2名(15%)为女性,12名(92%)为白人,1名(8%)为西班牙裔;平均年龄26岁 年(SD = 3.8年)。80个CpG被差异甲基化,实现了P的最小可能精确P值 = 2.44×10-4(即2/213)。在区域分析中,我们发现了两个注释在5号染色体开放阅读框63基因(C5orf63;7-CpG)和unc-45肌球蛋白伴侣A基因(UNC45A;5-CpG)上的差异甲基化区域(DMR)。DE暴露后,两种DMR均显示DNA甲基化增加。DMRs的平均因果效应范围为单个CpG的DNA甲基化增加1.5%至6.0%。总之,我们发现短期DE改变了靶支气管上皮细胞中基因的DNA甲基化,表明暴露的表观遗传学水平影响可能与肺部病理有关。
{"title":"Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells.","authors":"Andres Cardenas, Raj P Fadadu, Lars Van Der Laan, Cavin Ward-Caviness, Louis Granger, David Diaz-Sanchez, Robert B Devlin, Marie-Abèle Bind","doi":"10.1093/eep/dvab003","DOIUrl":"10.1093/eep/dvab003","url":null,"abstract":"<p><p>Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact <i>P</i>-value of <i>P </i>=<i> </i>2.44 × 10<sup>-4</sup> (<i>i.e.</i> 2/2<sup>13</sup>). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (<i>C5orf63</i>; 7-CpGs) and unc-45 myosin chaperone A gene (<i>UNC45A</i>; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/54/dvab003.PMC8035831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294144","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