Mechanisms driving multigenerational transmission of paternal stress in a new model

新模型中驱动父系压力多代传递的机制

• 批准号: 9753273
• 负责人: Jennifer K Hellmann
• 金额: $ 6.37万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753273
• 关键词: Address; Adolescent; Adult; Animals; Automobile Driving; Behavior; Behavioral; Behavioral Genetics; Biological Models; Child; Data; Development; Disease; Doctor of Philosophy; Embryo; Embryonic Development; Epigenetic Process; Evolution; Exposure to; Faculty; Fathers; Fellowship; Fertilization; Gasterosteidae; Gene Expression; Generations; Genomics; Germ Cells; Health; Hormonal; Human; Incubated; Individual; Inherited; Institution; Intervention; Laboratories; Maternal Exposure; Measures; Mediating; Mentors; MicroRNAs; Mission; Modeling; Modification; Molecular; Morphology; Mothers; Parents; Paternal Exposure; Personal Satisfaction; Phenotype; Physiological; Positioning Attribute; Post-Traumatic Stress Disorders; Predatory Behavior; Pregnancy; Public Health; Publications; RNA; Research; Risk; Smoking; Spermatogenesis; Stress; System; Testing; Training; Trauma; United States National Institutes of Health; Work; base; behavioral study; differential expression; experience; improved; individual variation; interest; male; nutrition; offspring; response; sex; skills; sperm cell; stressor; tenure track; training opportunity; transcriptome sequencing; transmission process; zygote

PROJECT SUMMARY Numerous studies in recent years have demonstrated that paternal experiences (e.g. smoking, nutrition, stress) prior to having children can influence the health, development, and behavior of the following generations. Existing studies exploring prefertilization paternal effects have been conducted in mammalian model systems, where it is difficult to isolate direct paternal influences on offspring from postfertilization maternal-offspring interactions. This project develops a new model for understanding the effects of stressors across generations: threespined sticklebacks (Gasterosteus aculeatus). Because sticklebacks have external fertilization, maternal influences can be teased apart from paternal influences. The applicant (Jennifer Hellmann) and her mentor (Dr. Alison Bell) will assess the influence of prefertilization paternal stress on embryonic development (Aim 1). They will also evaluate if the effects of paternal stress are transmitted across multiple generations by assessing if grandpaternal experiences can influence grandoffspring behavior and development (Aim 2). Finally, they will use embryonic manipulations to determine if sperm RNA is a mechanism underlying the epigenetic inheritance of paternal experiences (Aim 3). The project has relevance for human health because paternal stress in humans has multigenerational consequences, but there is a lack of understanding regarding the molecular mechanisms by which epigenetic modifications can be transmitted from one generation to the next. Further, predation risk in non- human animals is an ecologically relevant stressor that mirrors situations precipitating trauma (e.g. PTSD) in humans. This proposal will provide excellent training opportunities for the applicant (Jennifer Hellmann), whose long-term research interests center around understanding factors that promote individual variation in behavior and phenotype, including understanding the molecular mechanisms regulating phenotypic differences among individuals. The skills gained during her PhD work (behavioral, genetic, physiological) will provide a base from which to expand her research questions and Dr. Alison’s Bell laboratory group will provide an excellent avenue to gain the genomic research skills needed to address her long-term research interests. Further, this fellowship will provide mentoring opportunities, publications, and training that will better prepare the applicant for attaining a tenure-track faculty position at a research institution.

项目摘要 近年来的许多研究表明，父亲的经验（例如， 吸烟，营养，压力）在有孩子之前会影响健康，发展， 下一代的行为。现有的研究探索了优先化父亲效应 已经在哺乳动物模型系统中进行，其中难以分离直接父系的 受精后母子互动对后代的影响。这个项目 开发了一个新的模型来理解跨代压力源的影响： 三刺鱼（Gasterosteus aculeatus）。因为棘鱼有外部的 在受精过程中，母亲的影响可以与父亲的影响分开。 申请人（Jennifer Hellmann）和她的导师（Alison Bell博士）将评估 父方压力对胚胎发育的影响（目的1）。他们还将评估，如果 父亲压力的影响通过评估是否 祖父母的经历可以影响后代的行为和发展（目标2）。 最后，他们将使用胚胎操作来确定精子RNA是否是一种机制， 作为父系经验的表观遗传的基础（目的3）。该项目具有相关性 因为人类的父亲压力会产生多代人的后果， 关于表观遗传学的分子机制缺乏了解， 修改可以从一代传递到下一代。此外，在非- 人类动物是一种与生态学相关的应激源，反映了引发创伤的情况 (e.g. PTSD）在人类。 该提案将为申请人（Jennifer）提供绝佳的培训机会 赫尔曼），他的长期研究兴趣围绕着理解因素， 促进行为和表型的个体差异，包括理解分子生物学 调节个体间表型差异的机制。在她工作期间获得的技能 博士工作（行为学，遗传学，生理学）将提供一个基础，从其中扩大她的 研究问题和艾莉森博士的贝尔实验室小组将提供一个很好的途径， 获得解决她的长期研究兴趣所需的基因组研究技能。此外，本发明还 该奖学金将提供指导机会、出版物和培训， 为申请人在研究机构获得终身教职做好准备。