Creatine Synthesis and Transport in the Fetus - Critical Regulation of Energy Supply for Fetal Growth & Survival?

出生时的存活取决于婴儿是否能够有效地呼吸，是否能够保持足够的血液流向每个器官，以及大脑能否协调这些活动。其中任何一个失败都将导致死亡。在这项应用中，我们提出胎儿和新生儿获得足够肌酸供应的能力是生存所必需的，因为这种物质对于维持体内所有细胞的能量周转至关重要。在成年人中，肌酸要么从饮食中获得(从肠道吸收)，要么在肝脏合成和释放后获得。我们不知道胎儿组织是如何获得肌酸的，但我们知道，当肌酸过低时，胎儿很可能会死亡，如果母亲的饮食中补充了额外的肌酸，胎儿更有可能在出生时经历严重窒息。在这个项目中，我们将在怀孕的动物身上确定胎儿组织是否可以合成和吸收肌酸，以及在整个怀孕期间在母亲的饮食中提供额外的肌酸是否可以保护心脏、大脑和呼吸器免受窒息或低氧(缺氧)的损害。如果成功，我们将为孕妇开发一种新的治疗方法，保护她们未出生的婴儿免受出生窒息的危险。

Survival at birth depends on the baby being able to breathe effectively, to maintain adequate blood flow to every organ, and for the brain to coordinate these activities. Failure of any one of these will result in death. In this application we propose that the ability of the fetus and newborn baby to obtain adequate supplies of CREATINE is essential for survival, because this substance is essential for maintaining energy turnover in all cells in the body. In the adult, CREATINE is obtained either from the diet (after absorption from the gut), or after synthesis in, and release from the liver. We do not know how fetal tissues obtain CREATINE, but we do know that when CREATINE is too low the fetus is likely to die, and that if extra CREATINE is supplied in the mother's diet the fetus is more likely to survive profound asphyxia at birth. In this project, in pregnant animals we will determine if fetal tissues can synthesize and take up CREATINE, and if providing extra CREATINE in the maternal diet throughout pregnancy can protect the heart, brain and breathing apparatus from the damaging effects of asphyxia or low oxygen (hypoxia). If successful, we will have developed a new treatment for pregnant women that protects their unborn baby from the dangers of birth asphyxia.