Multi-generational Effects of Maternal Engineered Nano-Material Inhalation Exposure on Microvascular and Reproductive Health Outcomes

母体工程纳米材料吸入暴露对微血管和生殖健康结果的多代影响

• 批准号: 10525726
• 负责人: Elizabeth Compton Bowdridge
• 金额: $ 10.8万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525726
• 关键词: Multi; generational; Effects; Maternal; Engineered

PROJECT SUMMARY Elizabeth Bowdridge, Ph.D., is a reproductive toxicologist whose overarching career goal is to establish a successful laboratory focused on the effects of occupational and environmental factors on microvascular adaptations during gestation that ultimately impact fetal outcomes. Her proposed project combines an occupationally relevant inhalation exposure model during gestation and epigenetic analysis of offspring, which will establish the impact of hormones and vascular adaptations that are critical for healthy reproductive outcomes. Acquiring this knowledge is a critical step for ensuring optimal maternal and fetal health. Career Development Plan: Dr. Bowdridge is a Research Assistant Professor in the Department of Physiology and Pharmacology at West Virginia University (WVU). The proposed career development plan will build upon her previous training with four training goals to enhance her trajectory toward becoming an independent investigator: 1) Acquire advanced training in placental pathologies and identification of nanomaterials using techniques such as FESEM and TEM; 2) Broaden my knowledge of how the dose of specific toxicants are applicable in an occupational setting and ways in which these affect critical windows of embryonic and fetal developmental, oxidant formation, and epigenetics; 3) Increase technical expertise in occupational exposure relevance, dose deposition and epigenetic analysis across generations; 4) Develop professional skills in grant writing, research and laboratory leadership, statistical analysis, and research ethics. Mentors/environment: Dr. Bowdridge and her primary mentor, Dr. Timothy Nurkiewicz, Ph.D., have assembled a strong team of co-mentors and advisors to guide her through the proposed training and research activities. The proposed career development plan utilizes the intellectual, microscopy, free radical biology, and genomics resources available through WVU and at the National Institute for Occupational Safety and Health. The WVU Genomics and Bioinformatics cores provide centralized genomic and biostatistical analysis training to investigators at WVU and other universities across WV. As an institution WVU is committed to supporting junior faculty members through internal grants, administrative support and structured opportunities for faculty networking and education. Research: Adverse reproductive outcomes, such as miscarriages, are common in pregnant women working in occupational settings. These women are exposed to ENM such as, nano-titanium dioxide (nano-TIO2) via inhalation. One likely, but uninvestigated, way that ENM may mediate these poor outcomes in an occupational setting is by decreasing hormones critical pregnancy hormones such as estradiol (E2). This proposal is the first step in linking E2 and the peptide Kiss with vascular dysfunction and adverse reproductive outcomes due to occupationally relevant maternal nano-TiO2 inhalation exposure. Aim 1 identifies the roles of E2 and Kiss and oxidant load across timepoints in gestation on uterine microvascular function and fetal health following maternal nano-TiO2 inhalation exposure. Aim 2 determines the impact of maternal nano-TiO2 inhalation exposure on reproductive health of F1 female progeny. The completion of these aims will identify the roles of E2 and Kiss in establishing a healthy fetal environment by regulating vascular and endocrine function during occupational exposures.

项目摘要 伊丽莎白·鲍德里奇（Elizabeth Bowdridge）博士是一位生殖毒理学家，其总体职业目标是建立一个 成功的实验室专注于职业和环境因素对微血管的影响 妊娠期间的适应最终会影响胎儿结局。她提出的项目结合了一个 在妊娠和后代的表观遗传分析期间，与职业相关的吸入暴露模型 将建立激素和血管适应的影响，这对于健康生殖至关重要 结果。获取这些知识是确保最佳母亲和胎儿健康的关键步骤。 职业发展计划：Bowdridge博士是该系的研究助理教授 西弗吉尼亚大学（WVU）的生理学和药理学。拟议的职业发展计划将 在她以前的培训中以四个训练目标进行建立，以增强她成为一个轨迹 独立研究者：1）获得胎盘病理的高级培训和鉴定 纳米材料使用诸如FESEM和TEM等技术； 2）扩大我对剂量如何的了解 特定的有毒物质适用于职业环境以及这些影响影响关键窗户的方式 胚胎和胎儿发育，氧化剂形成和表观遗传学； 3）提高技术专业知识 世代相传的职业暴露相关，剂量沉积和表观遗传分析； 4）发展 授予写作，研究和实验室领导，统计分析和研究道德方面的专业技能。 导师/环境：Bowdridge博士和她的主要导师Timothy Nurkiewicz博士博士拥有 组建了一支强大的联席会员和顾问团队，以指导她完成拟议的培训和研究 活动。拟议的职业发展计划采用了智力，显微镜，自由基生物学以及 通过WVU和美国国家职业安全与健康研究所获得的基因组学资源。 WVU基因组学和生物信息学核心提供集中的基因组和生物统计分析培训 向WVU和WV的其他大学的调查人员致敬。由于机构致力于支持 通过内部赠款，行政支持和教师的结构性机会，初级教师 网络和教育。 研究：不良生殖结果，例如流产，在从事的孕妇中很常见 职业环境。这些妇女暴露于ENM，例如，通过 吸入。一种可能但未被调查的方式可以调节这些职业中这些糟糕的结果 设置是通过减少急症妊娠激素（例如雌二醇（E2））。该提议是第一个 将E2和肽亲吻与血管功能障碍和不良生殖结果联系起来的一步 职业相关的母体纳米-TIO2吸入暴露。 AIM 1标识E2和KISS的角色 在子宫微血管功能和胎儿健康上妊娠的氧化剂负载之后 母体纳米-TIO2吸入暴露。 AIM 2确定母体纳米-tio2吸入的影响 F1雌性后代的生殖健康暴露。这些目标的完成将确定 E2和亲吻在建立健康的胎儿环境中，通过调节血管和内分泌功能。 职业暴露。