A study of the pathophysiology and treatment in intrauterine growth retardation

1995 Fiscal Year Final Research Report Summary

• Project/Area Number: 06671166
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Nagoya University
• Principal Investigator: MIMURA Shunji Nagoya University School of Medicine, Research Assistant, 医学部, 助手 (30229794)
• Co-Investigator(Kenkyū-buntansha): HAYAKAWA Masahiro Nagoya University School of Medicine, Medical Staff, 医学部, 医員
• Project Period (FY): 1994 – 1995
• Keywords: Intrauterine Growth Retardation / Gestational Toxicosis / Central Nervous System Injury / Carbohydrate Metabolism / Energy Metabolism / Migration Disorders

Research Abstract

We studied biochemical and histopathological changes in the brain of intrauterine growth retardation (IUGR) using a model rat of IUGR induced by maternal administration of a synthetic thromboxane A_2 (STA_2). The weight and protein of the forebrain and brainstem decreased significantly in E20 IUGR fetus, whereas DNA content of the forebrain was higher in IUGR.Although pyruvate, lactate and glycogen reduced significantly in IUGR brain, glucose concentration in the brain tissue increased in IUGR.There were no significant differences in high-energy reserves, ATP,ADP,AMP and phosphocreatine between IUGR and control. These results implies organ and cellular growth failure with stimulated somatic mitoses in IUGR brain. Gluconeogenesis might compensate for chronic fetal hypoxia and decreased glycogen store. These changes may contribute to the phenomenon called "brain sparing", but energy metabolism in IUGR brain will be liable to be disrupted for the less reserve of energy substrates.
A histopathological study of IUGR brain was made from late fetal to early neonatal period. In E18 IUGR brain, abnormal clusters of differentiated nerve cells were found in the cortical plate. Cornal-sectioned area of E20 IUGR bain showed a significant reduction compared with that of the control, and ectopic clusters of differentiated cells cytologically mimicking neuroblasts were found in neuroepithelial layr. However, these abnormal clusters of cells in the fetal IUGR brain were not observed in PN7. Because the period of STA_2 administration coinsides well with the neurodevelopmental stage of cell migration and differentiation, the reduction of uteroplacental blood supply might cause transient abnormal cytoarchitecture of cerebral cortex in addition to brain growth retardation.