Maternal-fetal amino acid transfer across placenta in a mouse model of prenatal alcohol exposure

产前酒精暴露小鼠模型中母胎氨基酸跨胎盘转移

• 批准号: 10402658
• 负责人: Sze Ting Kwan
• 金额: $ 2.29万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402658
• 关键词: Address; Affect; Alcohol consumption; Alcohols; Amino Acid Transporter; Amino Acids; Award; Behavioral; Biological Process; Blood Circulation; Brain; Branched-Chain Amino Acids; COVID-19 pandemic; Catabolism; Child; Child Health; Chronic Disease; Clinical Research; Cognitive; Communities; Complex; Complication; Consumption; Data Set; Defect; Development; Diet; Dietary Intervention; Dietary Proteins; Down-Regulation; Effectiveness; Essential Amino Acids; Exhibits; Exposure to; FRAP1 gene; Fees; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal Development; Fetal Growth; Fetal Growth Retardation; Fetal Macrosomia; Fetal alcohol effects; Fetus; Functional disorder; Funding; Future; Genes; Health; Health Policy; Immunohistochemistry; Impaired cognition; Impairment; Individual; Institution; Intervention; Low Birth Weight Infant; Manuscripts; Mediating; Medical; Metabolic; Metabolism; Modernization; Mothers; Neurotransmitters; Nutrient; Outcome; Pathway interactions; Phosphorylation; Placenta; Population; Portraits; Pregnancy; Process; Production; Proteins; Public Health; Publishing; Regulatory Pathway; Reporting; Research; Schools; Signal Pathway; Signal Transduction; Study models; Supplementation; Techniques; Technology; Testing; Time; Tissue Harvesting; Western Blotting; after-school program; alcohol effect; alcohol exposure; amino acid metabolism; evidence base; experimental study; fetal; functional status; genetic risk factor; improved outcome; insight; mRNA sequencing; maternal alcohol use; metabolomics; mother nutrition; mouse model; neurobehavioral; novel; offspring; pandemic disease; postnatal; predictive marker; protein intake; relating to nervous system; research study; transcriptomics; uptake

Project Summary/Abstract The purpose for this supplement is to request a funded, 4-month extension for my current F32 award, from August 1st, 2021 to December 31st, 2021. Due to the COVID-19 pandemic, I was unable to continue performing experiments described in Aim 2 of my F32 project because the project under my current F32 award was not designated by my institution as essential research. Furthermore, I am a single mother with a young child, and the pandemic led to the shutdown of my child’s school and many afterschool programs in the local community. Without access to childcare, I had to spend a large amount of time homeschooling my child, which created an additional childcare responsibility and tremendous hardships that significantly hindered my research progress. The requested extension will compensate for the research time loss due to the pandemic, from March 2020 to July 2020. During this 4-month extension, I will complete the immunohistochemical experiments which investigate the cellular distribution of the amino acid (AA) transporters in the alcohol-exposed placentas, as described in Aim 2; these experiments would wrap up a manuscript. I will also finish analyzing the transcriptomic dataset generated from these alcohol-exposed placentas, another experiment described in Aim 2, for a second manuscript that is near-completion. The requested funds will cover my stipends during this 4- month extension period, research supplies needed to complete the immunohistochemistry, and fees for publishing the manuscripts reporting these results. The overall project hypothesis remains unchanged, which states that prenatal alcohol exposure (PAE) causes intrauterine growth restriction, at least in part, by reducing placental AA supply to the fetus, and that this is a consequence of downregulated placental mTOR signaling, AA transport, and altered AA metabolism. The three specific aims also remain unchanged. Aim 1 performs a comprehensive metabolomics analysis to characterize how PAE decreases AA supply and metabolic fate along the maternal-placental-fetal axis. Aim 2 performs transcriptomics analysis, western blotting and immunohistochemistry in the placenta to test the hypothesis that downregulation of placental AA transporters and metabolic genes contributes to the altered AA levels in PAE. Aim 3 performs western blotting in the placenta to test the hypothesis that these changes in AA transport and metabolism are accompanied by inhibition of placental mTOR pathways, which is a major regulator of AA availability and fetal growth. These studies use cutting-edge techniques to create a global portrait of how PAE affects placental AA supply and offer novel mechanistic insight into how PAE contributes to intrauterine growth restriction. The request extension will allow me to finish the proposed F32 research studies, which lay groundwork for future research that examines postnatal neural and metabolic health, the modulatory effect of genetic risk factors, and the effectiveness of maternal AA supplementation to improve outcomes of PAE pregnancies.

项目摘要/摘要 该补充的目的是要求我目前的F32奖励的4个月延长， 2021年8月1日至2021年12月31日。由于19日大流行，我无法继续 我的F32项目AIM 2中描述的执行实验是因为我当前的F32奖项项目 不是由我的机构设计为基本研究。此外，我是一个年轻的单身母亲 孩子，大流行导致我孩子的学校关闭和当地的许多课后课程 社区。没有获得托儿服务，我不得不花费大量时间在家上我的孩子，这 创造了额外的育儿责任和巨大的​​艰辛，这极大地阻碍了我的研究 进步。所请求的扩展将弥补由于大流行而导致的研究时间损失， 2020年3月至2020年7月。在这个4个月的延长期间，我将完成免疫组织化学实验 研究氨基酸（AA）转运蛋白在酒精暴露子宫结核中的细胞分布， 如AIM 2中所述；这些实验将结束手稿。我还将完成分析 来自这些酒精暴露的子宫结构产生的转录组数据集，AIM中描述的另一个实验 2，第二个手稿接近完成。要求的资金将弥补我在4-- 每月延长期，完成免疫组织化学所需的研究用品，并为 发布报告这些结果的手稿。总体项目假设保持不变，这是 指出产前酒精暴露（PAE）至少部分通过减少宫内生长限制 胎盘向胎儿供应，这是下调胎盘MTOR信号传导的结果， AA运输，并改变了AA代谢。这三个特定目标也保持不变。 AIM 1执行 综合代谢组学分析以表征PAE如何减少AA供应和代谢命运 AIM 2执行转录组学分析，蛋白质印迹和 plapeta中的免疫组织化学，以检验胎盘下调AA转运蛋白的假设 代谢基因促进了PAE中的AA水平的改变。 AIM 3在 lopeta检验以下假设：AA运输和代谢中的这些变化是通过 抑制胎盘MTOR途径，这是AA可用性和胎儿生长的主要调节剂。这些 研究使用尖端技术来创建全球肖像，说明PAE如何影响胎盘供应和 提供新的机械洞察力，以了解PAE如何有助于内在的生长限制。请求 扩展将使我能够完成拟议的F32研究，这为将来的研究奠定了基础 检查产后神经和代谢健康，遗传危险因素的调节作用以及 补充母体AA以改善PAE妊娠结局的有效性。