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: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-22 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7290359
• 关键词: Area; Blood Vessels; Cardiovascular Diseases; Cells; Chile; Coculture Techniques; Critical Pathways; DNA Methylation; Defect; Distance Education; Endometrial; Endometrium; Epigenetic Process; Event; Fertility; Fertilization in Vitro; Fetal Membranes; Functional disorder; Gelatinase A; Gene Proteins; Genes; Glucose Transporter; Human; Human Chorionic Gonadotropin; In Vitro; Inflammation; Insulin Resistance; Latin America; Life; MMP2 gene; Mentors; Messenger RNA; Metabolism; Obesity; Ovulation; Patients; Pattern; Pituitary Gland; Polycystic Ovary Syndrome; Pre-Eclampsia; Pregnancy; Premature Birth; Premature Labor; Progesterone; Progesterone Receptors; Reproductive Biology; Research; Research Training; Risk; Role; Rupture; Scientist; Signal Transduction; Smooth Muscle Myocytes; Spontaneous abortion; Steroid biosynthesis; TNF gene; Testing; Time; Tissues; Training; Translational Research; Tumor Necrosis Factor-alpha; Universities; Vascular Smooth Muscle; Virginia; Woman; base; cytokine; emergency contraception; gonorrhea vaccine; granulosa cell; granulose; human TNF protein; implantation; improved; in vivo; insight; neutrophil; ovulation time; prevent; receptor; receptor expression; vaccine development; vascular inflammation

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.

弗吉尼亚联邦大学（VCU）和智利大学将共同提供生殖生物学的转化研究培训，以年轻的科学家来自整个拉丁美洲。具体项目包括：1）中性粒细胞诱导的血管平滑肌基因表观遗传变化：目的是确定中性粒细胞或中性粒细胞产物（ROS、TNF？？）可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变化。这些研究的重要性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。将使用与活化中性粒细胞或中性粒细胞产物（ROS、TNF？？）共培养的人血管平滑肌细胞进行研究。为了检验血管平滑肌细胞暴露于嗜中性粒细胞、ROS或TNF-α将改变DNA甲基化模式导致与炎症相关的基因和蛋白质表达改变的假设。2)正常排卵患者LH峰值时和IVF患者hCG给药后卵泡颗粒细胞中孕激素受体（PR）的瞬时表达：本研究的目的是确定细胞因子是否选择性下调颗粒细胞的PR，并基于先前关于PR表达在排卵时的作用的体外和体内研究。 其中包括一项针对女性的研究， 从垂体释放LH峰诱导信号传导事件的快速级联，导致卵泡颗粒细胞中PRmRNA的表达。关于人类排卵调控基因的新发现可能为无排卵缺陷提供关键的见解，并为紧急避孕提供新的策略。3)PCOS妇女子宫内膜中的葡萄糖转运蛋白和基质金属蛋白酶2：有待检验的假设是PCOS妇女子宫内膜中葡萄糖转运蛋白和MMP 2表达的扭曲改变了子宫内膜代谢和组织重塑，这是建立接受性子宫内膜和维持早期妊娠的关键途径。 这项研究的发现对改善植入有意义由VCU和智利主持人领导的其他远程教育课程将涵盖培训导师所涵盖的研究领域，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，细胞信号传导，淋病疫苗开发，类固醇生成，促进健康怀孕。