Impacts of parental benzo[a]pyrene exposure on offspring’s bone development

父母接触苯并[a]芘对后代骨骼发育的影响

• 批准号: 10658133
• 负责人: Frauke Seemann
• 金额: $ 7.36万
• 依托单位: TEXAS A&M UNIVERSITY-CORPUS CHRISTI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658133
• 关键词: Address; Adult; Adverse effects; Applications Grants; Area; Aromatic Polycyclic Hydrocarbons; Award; Benzo(a)pyrene; Biomedical Research; Bone Density; Bone Development; Cell Differentiation process; Cell Lineage; Cells; Chemical Exposure; Communities; Complement; Complex; Conceptions; DNA Methylation; DNA Sequence; Data; Data Analyses; Defect; Deformity; Development; Disease; Dose; Elderly; Environment; Environmental Health; Environmental Risk Factor; Epidemic; Epigenetic Process; Exposure to; Gene Expression; Gene Expression Profile; Generations; Genes; Genetic; Health; Heritability; Hispanic; Histone Acetylation; Histones; Human; Immunohistochemistry; Impairment; Individual; Japanese Killifish; Knowledge; Life; Light; Long-Term Effects; Mentorship; MicroRNAs; Minority; Minority-Serving Institution; Mitotic; Modeling; Modification; Oryziinae; Osteoblasts; Osteoporosis; Osteoporotic; Parents; Pathology; Pattern; Persons; Phenotype; Physiologic calcification; Pollution; Population; Predisposition; Prevention strategy; Public Health; Regulation; Reporter; Research; Research Methodology; Research Project Grants; Risk; Risk Factors; Role; Science; Scientist; Sclerotome; Small RNA; Students; Testing; Therapeutic; Therapeutic Intervention; Toxicology; Transgenic Organisms; Underrepresented Students; Vertebral Bone; Work; bone; bone cell; bone fragility; bone health; bone loss; career; diagnostic tool; environmental stressor; experience; exposed human population; histone methylation; histone modification; improved; in utero; methylation biomarker; methylome; offspring; osteoblast differentiation; osteoporosis with pathological fracture; parent project; premature; progenitor; prognostic; recruit; response; skeletal; sound; tool; transcriptome; transcriptome sequencing; transcriptomics; undergraduate student

Biomedical research workforce diversity is critical for developing solutions for complex human health challenges. To address this issue, the recruitment, support, and mentorship of the M.S. thesis of a first- generation, Hispanic biomedical science student is one of the objectives of this research supplement to promote diversity in health-related research (following PA-21-071) in the framework of research conducted within the project “Impacts of parental benzo[a]pyrene exposure on offspring’s bone development” (1R15ES032936-01). The parent project aims to decipher the role of epigenetic mechanisms, DNA methylation, and microRNAs, in the development of parental benzo[a]pyrene (BaP) exposure-induced bone impairment. The present proposal will extend and complement this research by addressing histone modifications in larval and adult bone cells in a temporal and spatial manner. Using immunohistochemistry, the candidate will assess alterations for multiple histone acetylation and methylation markers resolving how parental BaP exposure is modulating the histone profile in the osteoblast cell lineage in the offspring. As a result, the student will obtain experience in an emerging area of biomedical sciences and toxicology research, shedding light on potential mechanisms through which ancestral BaP exposure elicits its effect on offspring bone health. This research will result in the identification of possible developmental markers for later life-stage osteoporosis risk. Moreover, a very passionate junior scientist from an underrepresented community will be equipped with state-of-the-art tools to pursue a career in biomedical sciences. Discriminating epigenetic marks and genes associated with cross-generational toxicology, the proposed research provides a platform for the development of prognostic/diagnostic tools to identify the risks of adverse effects of parental chemical exposure.

生物医学研究人员的多样性对于开发复杂的人类健康解决方案至关重要 挑战为了解决这个问题，招聘，支持，和指导的M.S.第一篇论文- 一代，西班牙裔生物医学科学的学生是这项研究的补充目标之一， 在研究框架内促进健康相关研究的多样性（遵循PA-21-071） 在“父母接触苯并[a]芘对后代骨骼的影响”项目范围内进行 开发”（1 R15 ES 032936 -01）。母项目旨在破译表观遗传的作用， 机制，DNA甲基化和microRNA，在父母苯并[a]芘（BaP）的发展 骨损伤。本建议将通过以下方式扩展和补充这项研究： 以时间和空间的方式解决幼虫和成体骨细胞中的组蛋白修饰。使用 免疫组织化学，候选人将评估多组蛋白乙酰化的改变， 甲基化标志物，解决了亲本BaP暴露如何调节组蛋白谱， 成骨细胞谱系。因此，学生将在新兴领域获得经验 生物医学科学和毒理学研究，揭示了潜在的机制， 祖先BaP暴露对后代骨健康的影响。这项研究将导致 确定可能的发育标志物为以后的生活阶段骨质疏松症的风险。此外，一个非常 来自代表性不足的社区的充满激情的年轻科学家将配备最先进的 工具，以追求在生物医学科学的职业生涯。区分表观遗传标记和相关基因 随着跨代毒理学，拟议的研究提供了一个平台， 预测/诊断工具，以确定父母接触化学品的不良影响的风险。

项目成果

The role of DNA methylation on gene expression in the vertebrae of ancestrally benzo[a]pyrene exposed F1 and F3 male medaka.

• DOI: 10.1080/15592294.2023.2222246
• 发表时间: 2023-12
• 期刊: EPIGENETICS
• 影响因子: 3.7
• 作者: Wan, Teng;Mo, Jiezhang;Au, Doris Wai-Ting;Qin, Xian;Tam, Nathan Yi-Kan;Kong, Richard Yuen-Chong;Seemann, Frauke
• 通讯作者: Seemann, Frauke

Assessment of parental benzo[a]pyrene exposure-induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish.

• DOI: 10.1093/eep/dvac013
• 发表时间: 2022
• 期刊: Environmental epigenetics
• 影响因子: 3.8