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Research Training in Epigenetics of Premature Labor, Progresterone Receptor Expre

Research Training in Epigenetics of Premature Labor, Progresterone Receptor Expre
早产表观遗传学研究培训,孕酮受体实验
批准号:
7290359
负责人:
JOHN E NESTLER
金额:
$13.41万
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-09-22 至 2011-03-31

项目摘要

项目成果

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中文摘要
翻译
弗吉尼亚联邦大学(VCU)和智利大学将联合向拉丁美洲各地的初级科学家提供生殖生物学方面的翻译研究培训。具体项目包括:1)中性粒细胞诱导血管平滑肌基因的表观遗传学改变:目的是确定中性粒细胞或中性粒细胞产物(ROS,TNF??)可以诱导与炎症和血管功能障碍相关的血管平滑肌基因的表观遗传学变化。这些研究的意义与肥胖和先兆子痫妇女在以后的生活中患心血管疾病的风险增加有关。研究将与激活的中性粒细胞或中性粒细胞产物(ROS,TNF??)共同培养人血管平滑肌细胞。为了验证这样一种假设,即血管平滑肌细胞暴露在中性粒细胞、ROS或TNF-α会改变DNA甲基化模式,导致与炎症相关的基因和蛋白质表达改变。2)正常排卵患者和体外受精患者应用hCG后卵泡颗粒细胞中孕酮受体(PR)的瞬时表达:本研究的目的是探讨细胞因子是否选择性地下调颗粒细胞的PR,并基于先前关于PR在排卵时的作用的体外和体内研究。这包括一项对女性的研究,该研究证实,垂体释放的黄体生成素高峰会引起一系列信号事件的快速级联,导致卵泡颗粒细胞中PR mRNA的表达。有关人类排卵调控基因的新发现可能会为无排卵缺陷提供关键的见解,并开发紧急避孕的新策略。3)多囊卵巢综合征患者子宫内膜中葡萄糖转运体和基质金属蛋白酶2的表达:有待检验的假说是多囊卵巢综合征患者子宫内膜葡萄糖转运体和MMP2表达的扭曲改变了子宫内膜的代谢和组织重塑,这是建立接受型子宫内膜和维持早孕的关键途径。这项研究的发现对改善PCOS的植入(从而提高生育率)和防止早期流产具有指导意义来自VCU和智利的演讲者领导的额外远程教育将涵盖培训导师涵盖的研究领域,包括多囊卵巢综合征和胰岛素抵抗、早产、先兆子痫、胎膜破裂、细胞信号、淋病疫苗开发、类固醇生成和促进健康怀孕。
英文摘要
Virginia Commonwealth University (VCU) and the University of Chile will jointly offer translational research training in reproductive biology to junior scientists from throughout Latin America. Specific projects include: 1) Neutrophil induced epigenetic changes in vascular smooth muscle genes: the aim is to determine if neutrophils or neutrophil products (ROS, TNF??) can induce epigenetic changes in vascular smooth muscle genes related to inflammation and vascular dysfunction. The significance of these studies relates to the increased risk obese and preeclamptic women have of developing cardiovascular disease later in life. Studies will be conducted with human vascular smooth muscle cells co-cultured with activated neutrophils or neutrophils products (ROS, TNF??) to test the hypothesis that exposure of vascular smooth muscle cells to neutrophils, ROS or TNF-alpha will alter the DNA methylation pattern resulting in altered expression of genes and proteins relating to inflammation. 2) Transient expression of the progesterone receptor (PR) in follicular granulosa cells at the time of LH peak in normal ovulatory patients and after hCG administration of IVF patients: the aim of this study is to determine if cytokines selectively down regulate PR of granulose cells, and are based on prior in vitro and in vivo studies regarding the role of PR expression at the time of ovulation. This includes a study in women confirming that the release of the LH surge from the pituitary induces a rapid cascade of signaling events resulting in the expression PR mRNA in granulosa cells of the follicle. New findings regarding genes regulating ovulation in humans may provide a key insight into anovulatory defects and to develop new strategies for emergency contraception. 3) Glucose transporters and matrix metalloproteinase 2 in the endometrium of women with PCOS: the hypothesis to be tested is that distortion of endometrial expression of glucose transporters and MMP2 in PCOS women alters endometrial metabolism and tissue remodeling, which are critical pathways for the establishment of a receptive endometrium and sustain an early pregnancy. Findings from this study have implications for improving implantation (and hence fertility) in PCOS and preventing early miscarriage Additional distance education offerings led by presenters from VCU and Chile will cover research areas covered by training mentors, including polycystic ovary syndrome and insulin resistance, preterm birth, pre-eclampsia, fetal membrane rupture, cell signaling, gonorrhea vaccine development, steroidogenesis, and promotion of healthy pregnancy.
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Translational Research in Polycystic Ovary Syndrome
  • 批准号:
    7932579
  • 项目类别:
  • 资助金额:
    $12.09万
  • 财政年份:
    2009
  • 负责人:
    JOHN E NESTLER
  • 依托单位:
DETERMINATION IF PHARMACOLOGIC BLOCKADE OF ANDROGEN ACTION DECREASES RENAL
  • 批准号:
    8166539
  • 项目类别:
  • 资助金额:
    $0.15万
  • 财政年份:
    2009
  • 负责人:
    JOHN E NESTLER
  • 依托单位:
DECREASE OF DCI AND DCI-IPG IN MUSCLE & OVARY IN PCOS & NORMAL WOMEN
  • 批准号:
    8166525
  • 项目类别:
  • 资助金额:
    $0.03万
  • 财政年份:
    2009
  • 负责人:
    JOHN E NESTLER
  • 依托单位:
METABOLIC SYNDROME IN AN ELDERLY POPULATION IS MORE LINKED TO INSULIN RES
  • 批准号:
    8166570
  • 项目类别:
  • 资助金额:
    $1.76万
  • 财政年份:
    2009
  • 负责人:
    JOHN E NESTLER
  • 依托单位:
海外基金