Analysis of pathophysiology of fetal central nerve injury and development for the method of evaluation

妊娠期胎儿中枢神经损伤的主要背景是宫内发育迟缓（IUGR）和早产。为了阐明氧化应激在IUGR发病机制中的作用，我们测定了羊水和胎盘基因组DNA样本中8-氧脱氧鸟嘌呤（8-OHdG）的含量。我们还检测了与核苷酸库中8OHdG的消除密切相关的酶mutt - t和muty的表达水平。IUGR组羊水中8OHdG浓度低于对照组，而胎盘染色体DNA中的8OHdG含量在两组之间相当。RT-PCR结果显示，IUGR组胎盘组织中Mut-T和Mut-Y mRNA表达水平较低，提示氧化应激对IUGR发病的影响更大的是胎儿，而不是胎盘。胎儿神经损伤的另一个背景应该是早产。子宫肌层中催产素受体的过早表达可能是早产的病理生理机制之一。为了阐明这种表达的机制，我们试图克隆催产素受体基因的DNA结合蛋白。从酵母单杂交筛选中获得鸡MafF同源基因hMafF，具有亮氨酸拉链结构，特异结合催产素受体基因。hMafF mRNA在足月子宫肌中特异性表达，而在早产儿子宫肌中的表达有待进一步研究。敲除小鼠模型也可能是研究早产机制的一个有吸引力的模型。我们对缺乏相关基因作为早产重要因素的小鼠的研究结果进行了文献综述。许多种类的敲除小鼠已经发育出来，尽管它们中的大多数在分娩时似乎是正常的，也就是说，对早产的调查没有提供信息。我们分析了胎儿神经损伤背景的几个因素。然而，我们未能在胎儿大脑中显示直接的病理生理关系。我们应该开发新的策略来直接评估胎儿大脑。少

The majour backgrounds for fetal central nerve injury during the course of pregnancy are intrauterine growth retardation (IUGR) and preterm birth. In order to elucidate the effect of oxidative stress on the pathogenesis of IUGR, we measured the amount of 8-oxodeoxyguanine (8-OHdG) in the samples of amniotic fluid and placental genomic DNA. We also examined the expression levels of enzymes Mut-T and Mut-Y, which deeply concern with elimination of 8OHdG from nucleotide pool. The concentration of 8OHdG in the amniotic fluid was lower in the IUGR group than control samples, whereas the 8OHdG amount in the placental chromosomal DNA was equivalent between two groups. The expression levels of Mut-T and Mut-Y mRNA, estimated by RT-PCR, were lower in the placental tissues of IUGR group These result suggested that fetus, rather than placenta are more affected by oxidative stress as pathogenesis of IUGR. Another background of fetal nerve injury should be preterm birth. One of pathophysiology of p … More reterm birth could be premature expression of oxytocin receptor in myometrium. To elucidate the mechanism of this expression, we attempted to clone DNA binding proteins to the oxytocin receptor gene. hMafF, a chicken MafF homologue, was obtained from Yeast one-hybrid screening which has the leucine zipper structure and binds specifically to the oxytocin receptor gene. hMafF mRNA as specifically expressed in term myometrium, whilst the expression during preterm myometrium should further be examined. The knock out mice model could also be an attractive model for investigation of the mechanism of preterm birth. We have literary reviewed the results of mice lacking the genes concerned as the important factor for preterm birth. Many kinds of knock out mice had developed, although most of them appears to be normal on their parturition, i. e., not informative for the investigation of preterm birth.We have analysed several factors for the background of fetal neurological injury. However, we failed to show the direct pathophysiological relationship within the fetal brain. We should develop novel strategy to evaluate fetal brain directly. Less