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

出生时的生存取决于婴儿能够有效地呼吸，保持足够的血液流向每个器官，以及大脑协调这些活动。任何一个失败都将导致死亡。在本申请中，我们提出，胎儿和新生儿获得充足肌酐供应的能力对于生存至关重要，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，肌酸可从饮食中获得（从肠道吸收后），或在肝脏中合成并释放后获得。我们不知道胎儿组织是如何获得肌酐的，但我们知道，当肌酐过低时，胎儿可能会死亡，如果母亲的饮食中提供额外的肌酐，胎儿在出生时更有可能在深度窒息中存活。在这个项目中，我们将在怀孕的动物中确定胎儿组织是否可以合成和摄取肌酐，以及在整个怀孕期间在母体饮食中提供额外的肌酐是否可以保护心脏，大脑和呼吸器官免受窒息或低氧（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.