Development of Human Endometrium for Embryonic Implantation

用于胚胎植入的人类子宫内膜的发育

• 批准号: 8519594
• 负责人: LINDA C GIUDICE
• 金额: $ 10.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8519594
• 关键词: Affect; Age; Assisted Reproductive Technology; Biological; Blood Vessels; Cell Lineage; Cell physiology; Cells; Conceptions; Development; Disease; Embryo; Endometrial; Endometrium; Epithelial; Fertility; Fibroblasts; Foundations; Future; Goals; Growth; Gynecologic; Healthcare Systems; Human; Human Development; Implant; Individual; Infertility; Instruction; Knowledge; Mediating; Medical; Messenger RNA; Modeling; Molecular; Mus; Natural regeneration; Operative Surgical Procedures; Pathogenesis; Pathway interactions; Patients; Pregnancy; Pregnancy Outcome; Progesterone; Public Health; Regulator Genes; Research; Retrograde Menstruation; Role; Stem cells; Symptoms; Tissues; Transplantation; Uterus; Woman; chronic pelvic pain; cost; effective therapy; endometriosis; implantation; novel; reproductive; stem

PROJECT SUMMARY (See instructions): PILOT PROJECT Endometriosis is one of the most common gynecologic disorders, affecting 10-15% of all reproductive age women, and specifically in 50-60% of women with chronic pelvic pain and infertility. Women with endometriosis have lower conception rates spontaneously or with assisted reproductive technologies. The cost of endometriosis to the U.S. healthcare system was $22 billion in 2002. Current options for women with endometriosis are limited to temporizing symptoms with either medical or surgical treatments. Retrograde menstruation was hypothesized as the primary cause. Molecular studies suggested that altered expression of regulatory genes in the eutopic endometrial tissue promotes implantation and growth of the ectopic endometrial cells. However, little is known about the changes in cellular function in the cellular components of the endometrium leading to the manifestation of endometriosis. Additionally, aberrant molecular pathways associated with endometriosis remain to be defined. Thus, there is a current gap of knowledge at both the cellular and molecular levels impeding the advancement of endometriosis research. Our long term goal is to identify the molecular pathways that promote endometriosis within each functional endometrial cell lineage and apply this knowledge to the development of novel and effective treatments for patients. Our current objective is to define the changes in cellular function in the individual endometrial cell lineage within the endometrium that promote endometriosis and to identify the lineage specific aberrant molecular pathways associated with this disease. Our aims are 1) to define the changes in cellular function of individual endometrial cell lineage that contribute to the pathogenesis of endometriosis using a mouse transplantation model that allows transplantation of mixtures of singly dissociated endometrial cells and 2) to identify and validate lineage-specific aberrant molecular pathways associated with endometriosis using paired mRNA/mlRNA profiles of highly purified lineage-specific primary and transplanted endometrial cells.

项目总结（见说明）：试点项目 子宫内膜异位症是最常见的妇科疾病之一，影响所有育龄妇女的10-15%，特别是50-60%患有慢性盆腔疼痛和不孕症的妇女。患有子宫内膜异位症的女性自发或辅助生殖技术的受孕率较低。2002年，子宫内膜异位症给美国医疗保健系统带来的成本为220亿美元。妇女目前的选择 子宫内膜异位症仅限于通过药物或手术治疗来缓解症状。月经逆行被假设为主要原因。分子生物学研究表明，在位子宫内膜组织中调控基因表达的改变促进了异位子宫内膜细胞的着床和生长。然而，子宫内膜细胞成分中细胞功能的变化导致子宫内膜异位症的表现知之甚少。此外，与子宫内膜异位症相关的异常分子通路仍有待确定。因此，目前在细胞和分子水平上的知识差距阻碍了子宫内膜异位症研究的进展。我们的长期目标是确定在每个功能性子宫内膜细胞谱系中促进子宫内膜异位症的分子通路 并将这些知识应用于为患者开发新颖有效的治疗方法。我们目前的目标是确定子宫内膜内促进子宫内膜异位症的单个子宫内膜细胞谱系中细胞功能的变化，并确定与这种疾病相关的谱系特异性异常分子通路。我们的目标是：1）确定个体细胞功能的变化， 使用小鼠移植模型，该模型允许移植单个解离的子宫内膜细胞的混合物，和2）使用高度纯化的谱系特异性原代和移植的子宫内膜细胞的配对mRNA/mRNA谱，鉴定和验证与子宫内膜异位症相关的谱系特异性异常分子途径。