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Erratum: Frequency of heavy vehicle traffic and association with DNA methylation at age 18 years in a subset of the Isle of Wight birth cohort. 勘误:在怀特岛出生队列的一个子集中,18岁时重型车辆交通频率与DNA甲基化的关系。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2019-03-20 eCollection Date: 2019-01-01 DOI: 10.1093/eep/dvz003
A Commodore, N Mukherjee, D Chung, E Svendsen, J Vena, J Pearce, J Roberts, S H Arshad, W Karmaus

[This corrects the article DOI: 10.1093/eep/dvy028.][This corrects the article DOI: 10.1093/eep/dvy028.].

[此更正文章DOI: 10.1093/eep/dvy028。][更正文章DOI: 10.1093/eep/dvy028.]。
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引用次数: 0
Dietary exposures, epigenetics and pubertal tempo. 饮食暴露、表观遗传学和青春期节奏。
IF 4.8 Q1 GENETICS & HEREDITY Pub Date : 2019-03-07 eCollection Date: 2019-01-01 DOI: 10.1093/eep/dvz002
Yue Wu, Brisa N Sánchez, Jaclyn M Goodrich, Dana C Dolinoy, Alejandra Cantoral, Adriana Mercado-Garcia, Edward A Ruiz-Narváez, Martha M Téllez-Rojo, Karen E Peterson

Gene expression changes mediated by DNA methylation may play a role in pubertal tempo regulation, and availability of methyl donor nutrients affects these pathways. We examined first trimester maternal and adolescent diet patterns that may be associated with DNA methylation at long interspersed nucleotide (LINE-1) repetitive elements in adolescence using least absolute shrinkage and selection operator (LASSO) and calculated an 'Epigenetics-Associated Diet Score' (EADS) for each pattern; then tested the associations of these scores with pubertal tempo among adolescent boys and girls. The analytic sample included 118 boys and 132 girls aged 10-18 years. DNA methylation at LINE-1 repetitive elements was quantified. Typical maternal and adolescent nutrient intakes were estimated using food frequency questionnaires. Interval-censored time to event and ordinal regression models were used to examine associations EADS scores with pubertal tempo using physician-assessed Tanner stages and self-reported menarche, respectively, adjusted for confounders. We observed associations between maternal EADS and pubertal onset, but not pubertal progression. Each standard deviation (SD) greater maternal EADS was associated with 52% higher odds of having later onset of menarche in both cross-sectional and prospective analysis (P = 0.031 and 0.028, respectively). In contrast, we observed associations between adolescent EADS and pubertal progression, but not pubertal onset. Among boys, for each SD higher adolescent EADS, there was 13% increase in odds of slower genital progression (P = 0.050), as well as 26 and 27% increase in odds of slower left and right testicular development, respectively (P = 0.001). Epigenetic-associated diet influences pubertal tempo in a sex- and timing-specific manner.

DNA 甲基化介导的基因表达变化可能在青春期节奏调节中发挥作用,而甲基供体营养素的可用性会影响这些途径。我们利用最小绝对收缩和选择算子(LASSO)研究了可能与青春期长穿插核苷酸(LINE-1)重复元素DNA甲基化相关的母体和青少年头三个月的饮食模式,并为每种模式计算了 "表观遗传学相关饮食评分"(EADS);然后测试了这些评分与青春期男孩和女孩青春期节奏的关联。分析样本包括 118 名男孩和 132 名女孩,年龄在 10-18 岁之间。对 LINE-1 重复元素的 DNA 甲基化进行了量化。利用食物频率问卷估算了母亲和青少年的典型营养摄入量。在对混杂因素进行调整后,我们分别利用医生评估的坦纳分期和自我报告的月经初潮,使用间隔删失的事件发生时间和序数回归模型来研究 EADS 分数与青春期节奏的关系。我们观察到母亲的 EADS 与青春期的开始有关联,但与青春期的进展无关。在横断面分析和前瞻性分析中,母亲EADS每增加一个标准差(SD),月经初潮推迟的几率就会增加52%(P = 0.031和0.028)。与此相反,我们观察到青春期 EADS 与青春期进展有关,但与青春期初潮无关。在男孩中,青春期 EADS 每增加一个标准差,生殖器发育较慢的几率就会增加 13%(P = 0.050),左侧和右侧睾丸发育较慢的几率也会分别增加 26% 和 27%(P = 0.001)。表观遗传相关饮食以性别和时间特异性的方式影响青春期节奏。
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引用次数: 0
Meeting Announcement: 2nd Symposium 'Epigenetic Inheritance: Impact for Biology and Society' 26-28 August 2019, ETH Zurich, Switzerland. 会议公告:第二届研讨会“表观遗传:对生物学和社会的影响”2019年8月26-28日,瑞士苏黎世联邦理工学院。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2019-02-07 eCollection Date: 2018-10-01 DOI: 10.1093/eep/dvz001
Isabelle M Mansuy
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引用次数: 0
Frequency of heavy vehicle traffic and association with DNA methylation at age 18 years in a subset of the Isle of Wight birth cohort. 怀特岛出生队列中18岁时重型车辆交通的频率和与DNA甲基化的相关性。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2019-01-23 DOI: 10.1093/eep/dvy028
A Commodore, N Mukherjee, D Chung, E Svendsen, J Vena, J Pearce, J Roberts, S H Arshad, W Karmaus

Assessment of changes in DNA methylation (DNA-m) has the potential to identify adverse environmental exposures. To examine DNA-m among a subset of participants (n = 369) in the Isle of Wight birth cohort who reported variable near resident traffic frequencies. We used self-reported frequencies of heavy vehicles passing by the homes of study subjects as a proxy measure for TRAP, which were: never, seldom, 10 per day, 1-9 per hour and >10 per hour. Methylation of cytosine-phosphate-guanine (CpG) dinucleotide sequences in the DNA was assessed from blood samples collected at age 18 years (n = 369) in the F1 generation. We conducted an epigenome wide association study to examine CpGs related to the frequency of heavy vehicles passing by subjects' homes, and employed multiple linear regression models to assess potential associations. We repeated some of these analysis in the F2 generation (n = 140). Thirty-five CpG sites were associated with heavy vehicular traffic. After adjusting for confounders, we found 23 CpGs that were more methylated, and 11 CpGs that were less methylated with increasing heavy vehicular traffic frequency among all subjects. In the F2 generation, 2 of 31 CpGs were associated with traffic frequencies and the direction of the effect was the same as in the F1 subset while differential methylation of 7 of 31 CpG sites correlated with gene expression. Our findings reveal differences in DNA-m in participants who reported higher heavy vehicular traffic frequencies when compared to participants who reported lower frequencies.

评估DNA甲基化(DNA-m)的变化有可能确定不良环境暴露。为了在参与者(n = 369),他们报告了可变的近居民交通频率。我们使用重型车辆经过研究对象家中的自我报告频率作为TRAP的替代指标,这些频率为:从不、很少、每天10次、每小时1-9次和每小时>10次。从18岁时采集的血液样本中评估DNA中胞嘧啶磷酸鸟嘌呤(CpG)二核苷酸序列的甲基化 年(n = 369)。我们进行了一项表观基因组范围的关联研究,以检查与重型车辆经过受试者家的频率相关的CpG,并使用多元线性回归模型来评估潜在的关联。我们在F2代(n = 140)。35个CpG站点与繁忙的车辆交通有关。在调整混杂因素后,我们发现在所有受试者中,随着重型车辆交通频率的增加,23个CpG的甲基化程度较高,11个CpG甲基化程度较低。在F2代中,31个CpG中的2个与交通频率相关,作用方向与F1亚群相同,而31个CpG位点中的7个的差异甲基化与基因表达相关。我们的研究结果显示,与报告较低频率的参与者相比,报告较高重型车辆交通频率的参与者的DNA-m存在差异。
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引用次数: 6
Simulated climate warming and mitochondrial haplogroup modulate testicular small non-coding RNA expression in the neotropical pseudoscorpion, Cordylochernes scorpioides. 模拟气候变暖和线粒体单倍群调节新热带拟蝎(Cordyochernes scorpioides)睾丸小的非编码RNA表达。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2018-12-24 DOI: 10.1093/eep/dvy027
Eleanor J Su-Keene, Melvin M Bonilla, Michael V Padua, David W Zeh, Jeanne A Zeh

Recent theory suggests that tropical terrestrial arthropods are at significant risk from climate warming. Metabolic rate in such ectothermic species increases exponentially with environmental temperature, and a small temperature increase in a hot environment can therefore have a greater physiological impact than a large temperature increase in a cool environment. In two recent studies of the neotropical pseudoscorpion, Cordylochernes scorpioides, simulated climate warming significantly decreased survival, body size and level of sexual dimorphism. However, these effects were minor compared with catastrophic consequences for male fertility and female fecundity, identifying reproduction as the life stage most vulnerable to climate warming. Here, we examine the effects of chronic high-temperature exposure on epigenetic regulation in C. scorpioides in the context of naturally occurring variation in mitochondrial DNA. Epigenetic mechanisms, including DNA methylation, histone modifications and small non-coding RNA (sncRNA) expression, are particularly sensitive to environmental factors such as temperature, which can induce changes in epigenetic states and phenotypes that may be heritable across generations. Our results indicate that exposure of male pseudoscorpions to elevated temperature significantly altered the expression of >60 sncRNAs in testicular tissue, specifically microRNAs and piwi-interacting RNAs. Mitochondrial haplogroup was also a significant factor influencing both sncRNAs and mitochondrial gene expression. These findings demonstrate that chronic heat stress causes changes in epigenetic profiles that may account for reproductive dysfunction in C. scorpioides males. Moreover, through its effects on epigenetic regulation, mitochondrial DNA polymorphism may provide the potential for an adaptive evolutionary response to climate warming.

最近的理论表明,热带陆生节肢动物面临着气候变暖的重大风险。这种外热物种的代谢率随着环境温度呈指数级增长,因此,在热环境中小幅升温比在冷环境中大幅升温具有更大的生理影响。在最近两项关于新热带拟蝎的研究中,模拟气候变暖显著降低了生存率、体型和两性异形水平。然而,与对男性生育能力和女性繁殖力的灾难性后果相比,这些影响很小,因为生殖是最容易受到气候变暖影响的生命阶段。在这里,我们在线粒体DNA自然发生变异的背景下,研究了长期高温暴露对天蝎类C.scorpioides表观遗传学调控的影响。表观遗传学机制,包括DNA甲基化、组蛋白修饰和小的非编码RNA(sncRNA)表达,对温度等环境因素特别敏感,这些因素可以诱导表观遗传学状态和表型的变化,这些变化可能会代代相传。我们的研究结果表明,雄性假蝎子暴露在高温下会显著改变睾丸组织中>60个sncRNA的表达,特别是微小RNA和piwi相互作用RNA。线粒体单倍群也是影响sncRNA和线粒体基因表达的重要因素。这些发现表明,慢性热应激会导致表观遗传学特征的变化,这可能是蝎子雄性生殖功能障碍的原因。此外,通过其对表观遗传学调控的影响,线粒体DNA多态性可能为气候变暖的适应性进化反应提供潜力。
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引用次数: 2
Fatherhood alters gene expression within the MPOA. 父亲角色会改变 MPOA 内的基因表达。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2018-12-12 eCollection Date: 2018-10-01 DOI: 10.1093/eep/dvy026
Adele M H Seelke, Jessica M Bond, Trent C Simmons, Nikhil Joshi, Matthew L Settles, Danielle Stolzenberg, Mijke Rhemtulla, Karen L Bales

Female parenting is obligate in mammals, but fathering behavior among mammals is rare. Only 3-5% of mammalian species exhibit biparental care, including humans, and mechanisms of fathering behavior remain sparsely studied. However, in species where it does exist, paternal care is often crucial to the survivorship of offspring. The present study is the first to identify new gene targets linked to the experience of fathering behavior in a biparental species using RNA sequencing. In order to determine the pattern of gene expression within the medial preoptic area that is specifically associated with fathering behavior, we identified genes in male prairie voles (Microtus ochrogaster) that experienced one of three social conditions: virgin males, pair bonded males, and males with fathering experience. A list of genes exhibiting different expression patterns in each comparison (i.e. Virgin vs Paired, Virgin vs Fathers, and Paired vs Fathers) was evaluated using the gene ontology enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathways analysis to reveal metabolic pathways associated with specific genes. Using these tools, we generated a filtered list of genes that exhibited altered patterns of expression in voles with different amounts of social experience. Finally, we used NanoString to quantify differences in the expression of these selected genes. These genes are involved in a variety of processes, with enrichment in genes associated with immune function, metabolism, synaptic plasticity, and the remodeling of dendritic spines. The identification of these genes and processes will lead to novel insights into the biological basis of fathering behavior.

哺乳动物必须由雌性来抚养,但哺乳动物中的父爱行为却很少见。包括人类在内,只有3-5%的哺乳动物会表现出双亲照顾的行为,而对父爱行为机制的研究仍然很少。然而,在存在父爱行为的物种中,父爱往往对后代的存活至关重要。本研究首次利用 RNA 测序技术在双亲物种中发现了与父爱行为相关的新基因靶点。为了确定内侧视前区内与父亲行为特别相关的基因表达模式,我们在经历了三种社会条件之一的雄性草原田鼠(Microtus ochrogaster)体内鉴定了基因:处女雄性、配对结合雄性和有父亲行为经验的雄性。我们使用基因本体富集分析和京都基因与基因组百科全书路径分析评估了在每种比较(即处男与配对、处男与父亲、配对与父亲)中表现出不同表达模式的基因列表,以揭示与特定基因相关的代谢路径。利用这些工具,我们筛选出了不同社会经验的田鼠体内表达模式发生改变的基因列表。最后,我们使用 NanoString 对这些选定基因的表达差异进行了量化。这些基因参与了多种过程,其中富含与免疫功能、新陈代谢、突触可塑性和树突棘重塑相关的基因。通过对这些基因和过程的鉴定,我们将对父亲行为的生物学基础有新的认识。
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引用次数: 0
Effect of a locally adapted genome on environmentally induced epigenetic variation. 局部适应基因组对环境诱导的表观遗传变异的影响。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2018-11-26 eCollection Date: 2018-10-01 DOI: 10.1093/eep/dvy025
France Beauregard, Bernard Angers

Both genetic variation and environmentally induced epigenetic changes allow organisms to persist through the heterogeneity of their habitats. Selection on genetic variation can promote local adaptation of populations. However, in absence of genetic variation, clonal organisms mostly rely on epigenetics to respond to environmental heterogeneity. We used the potential of unisexual organisms in incorporating their host genome, to empirically assess whether the presence of a locally adapted genome affects environmentally induced epigenetic changes in clonal organisms. We addressed this problematic by using unisexual lineages of the kleptogen vertebrate Ambystoma laterale-jeffersonianum complex that can optionally incorporate genetic material from locally adapted sexual hosts through genomic exchanges. More specifically, we compared environmentally induced epigenetic changes between lineages strictly reproducing clonally vs. those incorporating a locally adapted genome. The results revealed that both lineage and sample site components, as well as their interaction, affected epigenetic variation. When lineages were analysed separately, differences among sample sites were only detected in lineages impervious to genomic exchanges. Sample sites had no significant effect on the epigenetic variation of lineages that performed genomic exchanges. These results suggest that environmentally induced epigenetic variation among sites depends more on the lack of locally adapted alleles than on the level of genetic variation.

遗传变异和环境诱导的表观遗传变化都允许生物体在其栖息地的异质性中生存。遗传变异的选择可以促进群体的局部适应。然而,在没有遗传变异的情况下,克隆生物主要依靠表观遗传学来应对环境异质性。我们利用单性生物整合宿主基因组的潜力,以经验评估局部适应基因组的存在是否会影响克隆生物中环境诱导的表观遗传变化。我们通过利用窃食脊椎动物Ambystoma lateral -jeffersonianum复合体的单性谱系来解决这一问题,该复合体可以通过基因组交换选择性地结合来自当地适应性性宿主的遗传物质。更具体地说,我们比较了环境诱导的表观遗传变化之间的谱系严格复制与那些纳入本地适应基因组。结果表明,谱系和样品位点组分及其相互作用影响表观遗传变异。当谱系被单独分析时,样本位点之间的差异仅在不受基因组交换影响的谱系中被检测到。样本位点对进行基因组交换的世系的表观遗传变异没有显著影响。这些结果表明,环境诱导的位点间表观遗传变异更多地取决于缺乏局部适应的等位基因,而不是遗传变异的水平。
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引用次数: 3
Transgenerational inheritance of behavioral and metabolic effects of paternal exposure to traumatic stress in early postnatal life: evidence in the 4th generation. 父亲在产后早期暴露于创伤应激的行为和代谢影响的跨代遗传:第四代证据。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2018-10-16 eCollection Date: 2018-04-01 DOI: 10.1093/eep/dvy023
Gretchen van Steenwyk, Martin Roszkowski, Francesca Manuella, Tamara B Franklin, Isabelle M Mansuy
Abstract In the past decades, evidence supporting the transmission of acquired traits across generations has reshaped the field of genetics and the understanding of disease susceptibility. In humans, pioneer studies showed that exposure to famine, endocrine disruptors or trauma can affect descendants, and has led to a paradigm shift in thinking about heredity. Studies in humans have however been limited by the low number of successive generations, the different conditions that can be examined, and the lack of mechanistic insight they can provide. Animal models have been instrumental to circumvent these limitations and allowed studies on the mechanisms of inheritance of environmentally induced traits across generations in controlled and reproducible settings. However, most models available today are only intergenerational and do not demonstrate transmission beyond the direct offspring of exposed individuals. Here, we report transgenerational transmission of behavioral and metabolic phenotypes up to the 4th generation in a mouse model of paternal postnatal trauma (MSUS). Based on large animal numbers (up to 124 per group) from several independent breedings conducted 10 years apart by different experimenters, we show that depressive-like behaviors are transmitted to the offspring until the third generation, and risk-taking and glucose dysregulation until the fourth generation via males. The symptoms are consistent and reproducible, and persist with similar severity across generations. These results provide strong evidence that adverse conditions in early postnatal life can have transgenerational effects, and highlight the validity of MSUS as a solid model of transgenerational epigenetic inheritance.
在过去的几十年里,支持获得性性状跨代传播的证据重塑了遗传学领域和对疾病易感性的理解。在人类中,先驱研究表明,暴露于饥荒、内分泌干扰物或创伤会影响后代,并导致对遗传的思考范式转变。然而,对人类的研究受到了后代数量少、可以检查的不同条件以及它们所能提供的缺乏机械洞察力的限制。动物模型有助于规避这些限制,并允许在可控和可重复的环境中研究环境诱导性状的跨代遗传机制。然而,目前可用的大多数模型仅是代际的,并不能证明暴露个体的直系后代以外的传播。在这里,我们报告了在父亲产后创伤(MSUS)小鼠模型中,行为和代谢表型的跨代传递直到第四代。根据不同实验人员间隔10年进行的几次独立繁殖的大量动物(每组多达124只),我们发现,类似抑郁的行为会通过雄性遗传给后代,直到第三代,冒险和血糖失调会通过雄性遗传给第四代。这些症状是一致的和可重复的,并且在几代人中以相似的严重程度持续存在。这些结果提供了强有力的证据,表明出生后早期生活中的不利条件可能具有跨代影响,并强调了MSUS作为跨代表观遗传的坚实模型的有效性。
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引用次数: 75
Impacts of bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in the human placenta. 双酚A (BPA)和邻苯二甲酸盐暴露对人类胎盘表观遗传结果的影响。
IF 3.8 Q1 GENETICS & HEREDITY Pub Date : 2018-09-07 eCollection Date: 2018-07-01 DOI: 10.1093/eep/dvy022
Rita S Strakovsky, Susan L Schantz

The placenta guides fetal growth and development. Bisphenol A (BPA) and phthalates are widespread environmental contaminants and endocrine disruptors, and the placental epigenetic response to these chemicals is an area of growing research interest. Therefore, our objective was to summarize research linking BPA or phthalate exposure to placental outcomes in human pregnancies, with a particular focus on epigenetic endpoints. In PubMed, studies were selected for review (without limiting start date and ending on 1 May 2018) if they reported any direct effects of BPA or phthalates on the placenta in humans. Collectively, available studies suggest that BPA and phthalate exposures are associated with changes to placental micro-RNA expression, DNA methylation, and genomic imprinting. Furthermore, several studies suggest that fetal sex may be an important modifier of placental outcomes in response to these chemicals. Studies in humans demonstrate associations of BPA and phthalate exposure with adverse placental outcomes. Moving forward, more studies should consider sex differences (termed "placental sex") in the measured outcomes, and should utilize appropriate statistical approaches to assess modification by fetal sex. Furthermore, more consistent sample collection and molecular outcome assessment paradigms will be indispensable for making progress in the field. These advances, together with improved non-invasive tools for measuring placental function and outcomes across pregnancy, will be critical for understanding the mechanisms driving placental epigenetic disruption in response to BPA and phthalates, and how these disruptions translate into placental and fetal health.

胎盘引导胎儿生长发育。双酚A (BPA)和邻苯二甲酸盐是广泛存在的环境污染物和内分泌干扰物,胎盘对这些化学物质的表观遗传反应是一个日益增长的研究兴趣领域。因此,我们的目标是总结BPA或邻苯二甲酸盐暴露与人类妊娠胎盘结局之间的联系,特别关注表观遗传终点。在PubMed中,如果研究报告了双酚a或邻苯二甲酸盐对人类胎盘的任何直接影响,则选择研究进行审查(不限制开始日期,截止日期为2018年5月1日)。总的来说,现有的研究表明BPA和邻苯二甲酸盐暴露与胎盘微rna表达、DNA甲基化和基因组印记的变化有关。此外,一些研究表明胎儿性别可能是胎盘对这些化学物质反应的重要修饰因素。对人类的研究表明BPA和邻苯二甲酸盐暴露与胎盘不良结局有关。展望未来,更多的研究应该在测量结果中考虑性别差异(称为“胎盘性别”),并应该利用适当的统计方法来评估胎儿性别的改变。此外,更一致的样本收集和分子结果评估范式将是在该领域取得进展不可或缺的。这些进步,以及用于测量胎盘功能和妊娠结局的改进的非侵入性工具,将对理解双酚a和邻苯二甲酸盐对胎盘表观遗传破坏的反应机制,以及这些破坏如何转化为胎盘和胎儿健康至关重要。
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引用次数: 61
Pre-reproductive stress and fluoxetine treatment in rats affect offspring A-to-I RNA editing, gene expression and social behavior. 大鼠生殖前应激和氟西汀治疗会影响后代A-to-I RNA编辑、基因表达和社会行为
IF 4.8 Q1 GENETICS & HEREDITY Pub Date : 2018-08-08 eCollection Date: 2018-04-01 DOI: 10.1093/eep/dvy021
Hiba Zaidan, Gokul Ramaswami, Michal Barak, Jin B Li, Inna Gaisler-Salomon

Adenosine to inosine RNA editing is an epigenetic process that entails site-specific modifications in double-stranded RNA molecules, catalyzed by adenosine deaminases acting on RNA (ADARs). Using the multiplex microfluidic PCR and deep sequencing technique, we recently showed that exposing adolescent female rats to chronic unpredictable stress before reproduction affects editing in the prefrontal cortex and amygdala of their newborn offspring, particularly at the serotonin receptor 5-HT2c (encoded by Htr2c). Here, we used the same technique to determine whether post-stress, pre-reproductive maternal treatment with fluoxetine (5 mg/kg, 7 days) reverses the effects of stress on editing. We also examined the mRNA expression of ADAR enzymes in these regions, and asked whether social behavior in adult offspring would be altered by maternal exposure to stress and/or fluoxetine. Maternal treatment with fluoxetine altered Htr2c editing in offspring amygdala at birth, enhanced the expression of Htr2c mRNA and RNA editing enzymes in the prefrontal cortex, and reversed the effects of pre-reproductive stress on Htr2c editing in this region. Furthermore, maternal fluoxetine treatment enhanced differences in editing of glutamate receptors between offspring of control and stress-exposed rats, and led to enhanced social preference in adult offspring. Our findings indicate that pre-gestational fluoxetine treatment affects patterns of RNA editing and editing enzyme expression in neonatal offspring brain in a region-specific manner, in interaction with pre-reproductive stress. Overall, these findings imply that fluoxetine treatment affects serotonergic signaling in offspring brain even when treatment is discontinued before gestation, and its effects may depend upon prior exposure to stress.

腺苷到肌苷的RNA编辑是一种表观遗传过程,需要在作用于RNA的腺苷脱氨酶(ADARs)的催化下对双链RNA分子进行特定位点修饰。最近,我们利用多重微流控 PCR 和深度测序技术发现,让青春期雌性大鼠在繁殖前长期暴露于不可预测的压力下会影响其新生后代的前额叶皮层和杏仁核的编辑,尤其是5-羟色胺受体5-HT2c(由Htr2c编码)的编辑。在这里,我们使用同样的技术来确定应激后、生殖前母体使用氟西汀(5 毫克/千克,7 天)是否会逆转应激对编辑的影响。我们还检测了这些区域中ADAR酶的mRNA表达,并询问成年后代的社会行为是否会因母体暴露于应激和/或氟西汀而发生改变。母体使用氟西汀会改变出生后代杏仁核中的Htr2c编辑,增强前额叶皮层中Htr2c mRNA和RNA编辑酶的表达,并逆转生殖前应激对该区域Htr2c编辑的影响。此外,母体氟西汀治疗会增强对照组大鼠和应激暴露大鼠后代之间谷氨酸受体编辑的差异,并导致成年后代的社会偏好增强。我们的研究结果表明,妊娠前氟西汀治疗会以区域特异性的方式影响新生后代大脑中的RNA编辑和编辑酶表达模式,并与生殖前应激相互作用。总之,这些研究结果表明,即使在妊娠前停止治疗,氟西汀治疗也会影响后代大脑中的血清素能信号传导,而且其影响可能取决于之前所承受的压力。
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Environmental Epigenetics
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