Development of Human Endometrium for Embryonic Implantation

用于胚胎植入的人类子宫内膜的发育

基本信息

批准号：
9042859
负责人：
LINDA C GIUDICE
金额：
$ 35.24万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9042859
关键词：
Affect Age Assisted Reproductive Technology Biological Blood Vessels Cell Lineage Cell physiology Cells Characteristics Clinical Conceptions DNA Methylation Decidual Cell Reactions Development Disease Embryo Endometrial Endometrium Epigenetic Process Epithelial Fertility Fibroblasts Foundations Future Gene Expression Goals Growth Gynecologic Healthcare Systems Hormones Human Implant Individual Infertility Inherited Instruction Knowledge Link Mediating Medical Mesenchymal Stem Cells Messenger RNA Modeling Molecular Mus Natural regeneration Operative Surgical Procedures Outcome Pathogenesis Pathway interactions Patients Phenotype Pregnancy Pregnancy Complications Pregnancy Outcome Progesterone Public Health Regulator Genes Research Resistance Retrograde Menstruation Role Signal Pathway Stem cells Symptoms Testing Time Tissues Translations Transplantation Uterus Woman chronic pelvic pain cost cytotrophoblast effective therapy endometriosis epigenome epigenomics implantation novel prevent progenitor reproductive response stem stem cell differentiation steroid hormone targeted treatment tissue regeneration trophoblast

项目摘要

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.

项目摘要（请参阅说明）：试点项目子宫内膜异位症是最常见的妇科疾病之一，影响了所有生殖年龄妇女的10-15％，尤其是50-60％的慢性骨盆疼痛和不育的女性。子宫内膜异位症的妇女自发构想率较低或具有辅助生殖技术。 2002年，子宫内膜异位症的成本在2002年为220亿美元。子宫内膜异位症仅限于医疗或手术治疗的临时症状。假设逆行月经是主要原因。分子研究表明，在配音子宫内膜组织中调节基因的表达改变会促进异位子宫内膜细胞的植入和生长。然而，对于子宫内膜的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。另外，与子宫内膜异位有关的异常分子途径仍有待定义。因此，当前在细胞和分子水平上都存在一定的知识差距，这阻碍了子宫内膜异位研究的发展。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途径并将这些知识应用于患者的新颖和有效治疗的发展。我们目前的目标是定义子宫内膜中单个子宫内膜细胞谱系中细胞功能的变化，该子宫内膜促进子宫内膜异位症并确定与该疾病相关的谱系特异性异常分子途径。我们的目标是1）定义个体的细胞功能的变化 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.