Effects of paternal nicotine exposure on sncRNA expression in sire sperm and offspring hippocampus

父亲尼古丁暴露对父系精子及子代海马sncRNA表达的影响

• 批准号: 9910700
• 负责人: Dana Fuad Zeid
• 金额: $ 3.6万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9910700
• 关键词: Affect; Animals; Behavior; Behavioral; Biological; Biology; Brain; Bypass; Caring; Chronic; Complication; Conceptions; DNA Methylation; DNA Methylation Regulation; Data; Data Analyses; Data Set; Development; Drug Exposure; Embryo; Environmental Exposure; Epigenetic Process; Event; Exhibits; Experimental Designs; Exposure to; Expression Profiling; Foundations; Fright; Future; Gene Expression; Generations; Genetic Research; Genetic Transcription; Genome; Genomics; Goals; Health; Heritability; Hippocampus (Brain); Human; Inherited; Laboratories; Learning; Mediating; Memory; Messenger RNA; Modeling; Molecular; Mus; Nicotine; Outcome; Parents; Paternal Exposure; Pathway interactions; Pattern; Pharmaceutical Preparations; Phenotype; Physiological; Population; Role; Saline; Structure; Testing; Tissues; Translations; Untranslated RNA; Work; addiction; behavioral phenotyping; cholinergic; conditioned fear; design; drug of abuse; insight; mRNA Expression; male; neglect; nicotine exposure; nicotine use; novel; offspring; sperm cell; transmission process

PROJECT SUMMARY/ABSTRACT Recent evidence suggests that paternal drug exposure can affect behavioral and physiological phenotypes in unexposed offspring. In support, preliminary data from my laboratory indicates enhanced contextual fear conditioning and changes in hippocampal functioning in the offspring of nicotine-exposed male mice. This presents a potentially serious issue related to interpretation of data derived from both human and animal populations for which parental nicotine exposure was not taken into account. “Missing heritability” and discrepancies in heritability estimates between studies may be explained partially by variability in parental exposures. Characterization of mechanisms underlying this mode of inheritance, termed “multigenerational epigenetic inheritance,” is essential in order to compensate for these effects in experimental design and begin to understand exposure-specific multigenerational consequences. Other models of paternal drug exposure have pointed to inheritance through germline sncRNA expression as a potential underlying mechanism of multigenerational inheritance. In order to identify pathways underlying multigenerational effects of nicotine exposure on contextual fear learning, I will sequence sncRNA derived from sperm of male mice exposed to nicotine (F0) and the hippocampus of their offspring (F1). This data will be analyzed alongside our existing F1 hippocampus DNA methylation and mRNA expression datasets to reveal relationships between sncRNA expression in sperm and pathways underlying expression of multigenerational phenotypes in offspring. The proposed work will provide foundational insight into nicotine’s multigenerational effects, enriching current understanding of addiction heritability.

项目总结/摘要 最近的证据表明，父亲的药物暴露可以影响行为和生理表型， 未暴露的后代我实验室的初步数据表明， 暴露于尼古丁的雄性小鼠后代海马功能的调节和变化。这 提出了一个潜在的严重问题，涉及来自人类和动物的数据的解释 未考虑父母尼古丁暴露的人群。“遗传性缺失”， 研究间遗传力估计值的差异可能部分由双亲遗传力的变异性来解释。 暴露。这种遗传模式的机制被称为“多代遗传”， 表观遗传”对于在实验设计和开始中补偿这些影响至关重要 来理解特定的多代人的后果。父亲药物暴露的其他模型 已经指出通过种系sncRNA表达的遗传是遗传的潜在机制 多代遗传为了确定尼古丁多代效应的潜在途径， 暴露在情境恐惧学习中，我将测序来自暴露于环境恐惧的雄性小鼠精子的sncRNA。 尼古丁（F0）和其后代的海马体（F1）。这些数据将与我们现有的F1一起分析 海马DNA甲基化和mRNA表达数据集揭示sncRNA之间的关系 精子中的表达和后代中多代表型表达的潜在途径。的 拟议的工作将为尼古丁的多代效应提供基础性的见解， 对成瘾遗传性的理解。