Biochemical Development of the Fetus/Neonate and Maternal Diet

胎儿/新生儿和母亲饮食的生化发育

• 批准号: RGPIN-2016-04961
• 负责人: Koski, Kristine
• 金额: $ 2.26万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615408
• 关键词: Biochemical; Development; Fetus; Neonate; Maternal; Biochemical; Development; Fetus; Neonate; Maternal

Since its inception, my research program has investigated the biochemical development of the fetus and neonate with the overall goal of identifying nutritional and non-nutritional determinants of perinatal growth and organ development. Four novel experimental approaches have been used. These include (1) the characterization of the nutrient composition of amniotic fluid (AF) which is continuously swallowed by the growing fetus and may provide an important first window into the early biochemical development of the fetus; (2) an exploration of novel bioactive, components in milk, including but not limited to inflammatory markers and cytokines, and their impact on postnatal growth and development; and (3) an investigation into mechanisms by which gastrointestinal nematode infections when coupled with nutritional deficiencies impair perinatal growth and organ development. During the tenure of my last NSERC grant, each approach resulted in new insights. First, evidence emerged to show that albumin, the major protein in AF, can be irreversibly oxidized, suggesting an important but underappreciated role for dietary antioxidants early in pregnancy. Secondly maternal protein deficiency and infection impaired immune development by increasing pro-inflammatory cytokines and lowering concentrations of growth factors in plasma and in milk. Thirdly protein deficiency and infection impaired fetal and neonatal growth and organ development differently and these differences were associated with important compartmental changes in concentrations of cortisol, growth factors, proinflammatory cytokines in plasma, amniotic fluid and in milk. The overarching goal of the current discovery grant is to continue to explore the biochemical determinants of perinatal growth and development with following specific aims: AIM 1: The first aim will explore how amniotic fluid nutrients and newly emerging bioactive constituents (miRNAs, EPO, cytokines and growth factors) contribute to the regulation of early fetal growth. A secondary approach is to explore if oxidative stress itself impairs fetal growth or will the presence of dietary antioxidants in AF be of some benefit? AIM 2: Mastitis, an asymptomatic breast inflammation, is associated with changes in the milk microbiome, increased milk cytokines and impaired growth. We will explore if inflammation induced changes in milk composition (nutrients/growth & immune factors, microbiome) impair neonatal growth. AIM 3: The third aim explores how inflammation and immunity, commonly associated with gastrointestinal nematode infections and maternal protein deficiency, impact perinatal organ development. A secondary objective is to determine if these changes occur through alterations in the intestinal microbiome and/or differential expression on gene transcripts in developing fetal and neonatal organ systems?

自成立以来，我的研究计划研究了胎儿和新生儿的生化发展，其总体目标是鉴定围产期生长和器官发育的营养和非核心决定因素。已经使用了四种新型实验方法。其中包括（1）羊水（AF）的营养成分的表征，该营养成分被不断增长的胎儿不断吞噬，并可能为胎儿早期生物化学发育提供重要的第一窗口； （2）对新型生物活性，牛奶中的成分的探索，包括但不限于炎症标记和细胞因子及其对产后生长和发育的影响； （3）研究胃肠线虫感染与营养缺乏症相结合的机制的调查会损害围产期生长和器官发育。 在我上次NSERC赠款任职期间，每种方法都会产生新的见解。首先，有证据表明，白蛋白是AF中的主要蛋白质，可以被不可逆地氧化，这表明妊娠初期饮食抗氧化剂的重要但不足的作用。其次，孕产妇蛋白缺乏和感染通过增加促炎性细胞因子并降低血浆和牛奶中生长因子浓度而受损。第三，蛋白质缺乏和感染受损的胎儿和新生儿生长和器官发育不同，这些差异与皮质醇浓度，生长因子，血浆中的促炎细胞因子，羊水和牛奶中的重要隔室变化有关。 当前发现补助金的总体目标是继续探索围产期生长和发育的生物化学决定因素，具有以下特定目的：目标1：第一个目标将探讨如何促进羊水的养分以及新出现的生物活性成分（miRNA，EPO，EPO，细胞力和细胞因子和生长因素），从而对早期胎儿的生长有影响。一种次要方法是探索氧化应激本身是否会损害胎儿的生长，还是在AF中存在饮食中的抗氧化剂会有某种益处吗？ AIM 2：乳腺炎是一种无症状的乳腺炎，与牛奶微生物组的变化，牛奶细胞因子增加和生长受损有关。我们将探索炎症是否诱发牛奶成分（营养/生长和免疫因子，微生物组）的变化会损害新生儿的生长。目标3：第三个目标探讨了炎症和免疫，通常与胃肠线虫感染和母体蛋白质缺乏，影响围产期器官发育有关。次要目标是确定这些变化是否是通过在发展​​胎儿和新生儿器官系统中的基因转录物上的肠道微生物组和/或差异表达发生的？