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 本附录的目的是请求为我目前的F32奖延长4个月的资金，从 2021年8月1日至2021年12月31日。由于新冠肺炎的流行，我无法继续下去 执行我的F32项目的目标2中描述的实验，因为我当前的F32奖项下的项目 没有被我的机构指定为基本研究。此外，我是一位单身母亲，有一个年幼的 孩子，大流行导致我孩子的学校停课，当地的许多课外项目 社区。由于没有托儿所，我不得不花大量时间在家教育我的孩子，这 造成了额外的育儿责任和巨大的困难，这严重阻碍了我的研究 进步。所要求的延期将补偿大流行造成的研究时间损失，从 2020年3月至2020年7月。在这4个月的延长期内，我将完成免疫组织化学实验 研究了酒精暴露的胎盘中氨基酸转运体的细胞分布， 如目标2所述，这些实验将完成一份手稿。我还将完成对 从这些酒精暴露的胎盘生成的转录数据集，另一项实验在AIM中描述 2、即将完成的第二份手稿。申请的资金将用于支付我这4年的津贴- 一个月的延长期，完成免疫组织化学所需的研究用品，以及 发表报道这些成果的稿件。总体项目假设保持不变，即 声明产前酒精暴露(PAE)至少在一定程度上通过减少 胎盘AA供应给胎儿，这是胎盘mTOR信号下调的结果， AA转运，改变了AA代谢。三个具体目标也保持不变。AIM 1执行一个 综合代谢组学分析研究PAE如何减少AA供应和代谢命运 沿着母体-胎盘-胎儿轴。AIM 2进行转录分析，Western blotting和 胎盘AA转运蛋白下调的免疫组织化学研究 代谢基因导致PAE中AA水平的改变。AIM 3执行Western blotting中的 以检验这样一种假设，即这些AA运输和代谢的变化伴随着 抑制胎盘mTOR通路，这是AA可获得性和胎儿生长的主要调节因素。这些 研究使用尖端技术来创建PAE如何影响胎盘AA供应和 对PAE如何导致宫内生长受限提供了新的机械论见解。该请求 延期将使我能够完成拟议的F32研究，为未来的研究奠定基础 它检查出生后的神经和代谢健康，遗传风险因素的调节作用，以及 补充母体AA改善PAE妊娠结局的有效性。