Fetal endotoxin exposure and regulation of amino acid supply

胎儿内毒素暴露与氨基酸供应的调节

• 批准号: 341265-2012
• 负责人: Regnault, Timothy
• 金额: $ 1.97万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572213
• 关键词: Fetal; endotoxin; exposure; regulation; amino

Maternal dietary, environment and pathogen-induced stress during pregnancy are important factors contributing to in utero growth, survival after birth and postnatal health. In particular, pathogen-induced bacterial infections result in significant losses to agriculture. Treatment of healthy pregnant animals with bacterial cell wall components, termed lipopolysaccharide (LPS) provides an important approach for modeling how infection adversely affects pregnancy outcomes. Exposure to LPS in fetal life, results in low birth weight and animal losses. Additionally, in postnatal animals, LPS exposure affects skeletal muscle development providing a basis for reduced protein development; however how LPS infection during fetal development may impact future muscle growth capacity, have not been clearly defined. Lysine is an essential amino acid required for fetal development and growth. Perturbations to the system of lysine supply from mother to fetus and into the fetuses' developing tissue beds, (e.g., fetal muscle) adversely affect growth potential. During pregnancy, circulating levels of lysine are increased in animal fetal preparations associated with low birth weight. This suggests that there is potentially an outward movement of lysine (thereby reducing muscle development) occurring from fetal tissues during conditions associated with the development of low birth weight animals. The promotion of this movement occurs possibly through the activation of a lysine amino acid transporter component under a LPS challenge. This activation sets the scene for reduced protein development, as a result of substrate loss, together with stress induced protein building machinery inactivation in fetal life. This presents a significant problem for sustained muscle growth and development in postnatal life. Our work is aimed at understanding how infections alter fetal muscle development. The outcomes will define the molecular mechanisms regulating fetal protein dynamics following LPS treatment and thus probe the basic mechanisms underlying fetal muscle loss and or future growth potential following infection during pregnancy, which is a significant economical problem facing livestock production facilities.

孕期母亲的饮食、环境和病原体引起的应激是影响子宫内生长、出生后存活和产后健康的重要因素。特别是病原体引起的细菌感染给农业造成重大损失。用细菌细胞壁成分（称为脂多糖（LPS））治疗健康怀孕动物，为模拟感染如何对妊娠结局产生不利影响提供了重要方法。胎儿时期接触 LPS 会导致低出生体重和动物死亡。此外，在出生后的动物中，LPS 暴露会影响骨骼肌发育，从而为蛋白质发育减少提供基础；然而，胎儿发育期间的 LPS 感染如何影响未来的肌肉生长能力尚未明确。赖氨酸是胎儿发育和生长所需的必需氨基酸。从母亲到胎儿以及胎儿发育组织床（例如胎儿肌肉）的赖氨酸供应系统的扰动会对生长潜力产生不利影响。怀孕期间，与低出生体重相关的动物胎儿制剂中赖氨酸的循环水平增加。这表明在与低出生体重动物发育相关的条件下，胎儿组织中的赖氨酸可能会向外移动（从而减少肌肉发育）。这种运动的促进可能是通过在 LPS 攻击下激活赖氨酸氨基酸转运蛋白成分而发生的。这种激活为底物损失以及胎儿生命中应激诱导的蛋白质构建机制失活导致蛋白质发育减少奠定了基础。这对出生后的持续肌肉生长和发育提出了一个重大问题。我们的工作旨在了解感染如何改变胎儿肌肉发育。结果将定义 LPS 治疗后调节胎儿蛋白质动态的分子机制，从而探讨妊娠期间感染后胎儿肌肉损失和/或未来生长潜力的基本机制，这是畜牧生产设施面临的一个重大经济问题。