Search

Fetal growth restriction (FGR) remains a cause of perinatal brain injury, sometimes leading to neurological and intellectual impairment. Although the mechanisms and pathophysiology of CNS injuries have not been elucidated completely, it is possible carbohydrate and energy metabolism may have an important role in the FGR brain. In this study, FGR was induced in rats by administration of synthetic thromboxane A2 (STA2). Pups were delivered by cesarean section. After killing, samples were obtained from the fetuses of both control and FGR rats for evaluation of carbohydrate and energy metabolism in brain tissue. Lactate and pyruvate levels in brain were reduced significantly in the FGR group. Glucose content in brain tissue tended to be increased in the FGR group. In contrast, glycogen content in brain tissue tended to be lower in the FGR group. However, these differences in glucose and glycogen content did not reach statistical significance. Brain high-energy reserves, including ATP, ADP, AMP, and phosphocreatine (P-Cr), were similar in the control and FGR groups. Gluconeogenesis compensated for chronic fetal hypoxia and decreased glycogen storage. Energy metabolism in the FGR brain is likely to be disrupted as a consequence of lower reserves of energy substrates.

Intrauterine growth retardation (IUGR) is an important cause of prenatal and neonatal morbidity, and neurologic abnormalities. Although several animal models of IUGR have been developed for scientific investigation, few models approximate the pathophysiology in human fetal growth failure resulting from pregnancy-induced hypertension and preeclampsia. We developed an animal model of IUGR in which fetal growth restriction was induced by administering a synthetic thromboxane A(2) analogue (STA(2)) to the mother.Timed pregnant Sprague-Dawley rats were used in this study. STA(2) was delivered into the peritoneal cavity of the pregnant female at a rate of 20 ng/h from day 13 of pregnancy. The effectiveness of this model was evaluated by monitoring the overall growth of the fetuses and neonates and measuring the weight and biochemical composition of individual organs.Fetuses and neonates from the STA(2) group showed a highly significant weight reduction throughout the observation period from day 19 of gestation to postnatal day 7. Weight reduction near and at term exceeded 10% and became more pronounced during the first week after birth. Fetuses on the 20th gestational day exhibited a pattern of growth retardation characteristic of asymmetrical IUGR in which the weight reduction was prominent in the liver with relative sparing of the brain. However, the decrease in brain weight was more than 10%. The protein, DNA, and RNA contents of the liver were lower in the STA(2) group. The protein content of the forebrain and brainstem also decreased significantly in the STA(2) group compared with the control; however, the DNA content of the forebrain was higher in the STA(2) group.This animal model may mimic human IUGR more closely than previous models because the growth restriction is induced in a truly chronic manner.