• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >The roles of the placenta and oxidative stress in the pathogenesis of pre-eclampsia in a novel genetic mouse model.
【24h】

The roles of the placenta and oxidative stress in the pathogenesis of pre-eclampsia in a novel genetic mouse model.

机译：在新型遗传小鼠模型中，胎盘和氧化应激在先兆子痫发病机理中的作用。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pre-eclampsia is a very serious disease of pregnancy that is surprisingly common. In spite of its prevalence and potentially devastating consequences, little is known about the pathophysiology of pre-eclampsia, in part due to the lack of animal models which develop the disease spontaneously. We hypothesized that BPH/5, an inbred mouse strain with mildly elevated basal blood pressure would develop pre-eclampsia in pregnancy, because modest elevations in blood pressure prior to pregnancy strongly predispose women toward the development of pre-eclampsia. We discovered that BPH/5 show the diagnostic criteria of pre-eclampsia, hypertension and proteinuria in late pregnancy, and exhibit poor fetal outcomes, another hallmark of pre-eclampsia in women. In light of the two-stage model of pre-eclampsia, which suggests that the placenta is the source of the disease, we hypothesized BPH/5 placentas would exhibit developmental abnormalities prior to the onset of maternal symptoms. In fact placentas of BPH/5 do exhibit severe histomorphic changes in parallel with marked dysregulation of key trophoblast genes and genes related to lipid metabolism and oxidative stress. Because of these findings, and emerging evidence from the clinical literature showing a role for reactive oxygen species (ROS) in pre-eclampsia, we hypothesized that placental dysfunction in BPH/5 was due to increased oxidative stress in the placenta. We discovered that a key antioxidant enzyme is deficient in BPH/5 placenta which is associated with increased placental ROS. To establish a causal role for oxidative stress in this model, BPH/5 were treated with the antioxidant Tempol. Treatment of BPH/5 with Tempol completely abolished late-gestational maternal symptoms and significantly improved feto-placental outcomes. In addition to a role for oxidative stress in the placenta, studies in isolated mesenteric vessels showed that increased ROS also leads to maternal vascular dysfunction. Finally, uterine transfer of BPH/5 embryos into C57 surrogates demonstrated that poor placental development was the product of feto-placental genetics and not the cardiovascular phenotype of the mother. Collectively, these studies provide new insights into the role of the placenta in pre-eclampsia and show a causal role for ROS in the pathogenesis of the disease.
机译：子痫前期是一种非常严重的妊娠疾病，出奇地常见。尽管其流行和潜在的破坏性后果，但对先兆子痫的病理生理学知之甚少，部分原因是缺乏能自发发展该疾病的动物模型。我们假设BPH / 5（一种基础血压轻度升高的近交小鼠品系）在怀孕时会发展先兆子痫，因为怀孕前血压的适度升高强烈地促使女性倾向于先兆子痫。我们发现BPH / 5可以显示妊娠晚期子痫前期，高血压和蛋白尿的诊断标准，并且胎儿预后差，这是妇女子痫前期的另一个标志。鉴于先兆子痫的两阶段模型表明胎盘是疾病的根源，我们假设BPH / 5胎盘在母亲症状发作之前会出现发育异常。实际上，BPH / 5的胎盘确实表现出严重的组织形态变化，同时与关键的滋养层基因以及与脂质代谢和氧化应激相关的基因显着失调。由于这些发现，以及临床文献中新出现的证据表明先兆子痫中活性氧（ROS）的作用，我们假设BPH / 5中的胎盘功能障碍是由于胎盘中的氧化应激增加所致。我们发现一种关键的抗氧化酶缺乏BPH / 5胎盘，与胎盘ROS增加有关。为了在该模型中建立氧化应激的因果关系，将BPH / 5用抗氧化剂Tempol处理。用Tempol治疗BPH / 5完全消除了孕晚期孕妇的症状，并显着改善了胎盘胎盘的预后。除了在胎盘中氧化应激的作用外，在离体肠系膜血管中进行的研究还表明，ROS升高还会导致孕妇血管功能障碍。最后，子宫的BPH / 5胚胎向C57代孕的转移表明胎盘发育不良是胎儿胎盘遗传学的产物，而不是母亲的心血管表型。总体而言，这些研究为胎盘在先兆子痫中的作用提供了新的见解，并显示了ROS在疾病发病机理中的因果作用。

著录项

  • 作者

    Hoffmann, Darren Samuel.;

  • 作者单位

    The University of Iowa.;

  • 授予单位 The University of Iowa.;
  • 学科 Health Sciences Obstetrics and Gynecology.; Biology Physiology.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 211 p.
  • 总页数 211
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 妇幼卫生;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号