GENE EXPRESSION IN ENDOMETRIOSIS

子宫内膜异位症的基因表达

• 批准号: 6073964
• 负责人: JANET A. WARRINGTON
• 金额: $ 10万
• 依托单位: AFFYMETRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6073964
• 关键词: Scandinavian country; cell type; endometriosis; female; gene expression; human subject; menstrual cycle; microarray technology; oligonucleotides; peritoneum; technology /technique development; uterus neoplasms

Genes drive the biological functions that characterize and distinguish tissue types. The levels and timing of gene expression govern cellular development, differentiation, function and physiology. In an effort to better understand the etiology of endometriosis, a disease affecting 10% of all women of child bearing age, we are studying the genes expressed in unaffected and endometriosis-affected women. Normal endometrium consists of proliferative, secretory and glandular epithelia, and stromal and vascular elements. The epithelial cells synchronously proliferate, then differentiate and disintegrate at 28 day intervals. Proliferation is the dominant activity during days 4-13 of the menstrual cycle. During the proliferative phase the endometrium thickens and is characterized by mitoses within the glandular epithelium and pseudostratification of nuclei. After ovulation occurs the secretory phase begins (days 14-28) characterized first by basal vacuolation and secretion in glandular epithelium and later stromal edema and predecidual reaction. Until recently it has not been possible to simultaneously and quantitatively measure the expression levels of the thousands of human genes that characterize endometrial tissue and that distinguish normally functioning tissue from disease affected tissue. Using GeneChip(R) probe array (chip) technology we are able to simultaneously measure the relative concentrations of thousands of mRNAs in a single experiment. In Phase 1 using chips containing probes for approximately 7200 human genes we will: 1) Identify genes expressed in normal endometrium during the proliferative phase of the human menstrual cycle. 2) Identify stage I-IV endometriosis associated gene expression differences in proliferative endometrium. 3) Identify expression differences associated with endometriosis stage II, III, and IV proliferative endometrium, peritoneal lesions and ovarian endometriomas using matched samples. Only recently, with the development of the oligonucleotide array technology for gene expression monitoring, has a project of this scope become feasible. PROPOSED COMMERCIAL APPLICATIONS: NONE AVAILABLE

基因驱动表征和区分组织类型的生物功能。基因表达的水平和时间决定细胞的发育、分化、功能和生理。为了更好地了解子宫内膜异位症的病因，一种影响10%育龄妇女的疾病，我们正在研究未受影响和子宫内膜异位症影响的妇女中表达的基因。正常子宫内膜由增生上皮、分泌上皮、腺上皮、间质和血管组成。上皮细胞同步增殖，然后分化和解体，在28天的时间间隔。增殖是月经周期第4-13天的主要活动。在增殖期，子宫内膜增厚，其特征是腺上皮内有丝分裂和细胞核假分层。排卵后，分泌期开始（第14-28天），其特征首先是腺上皮的基底空泡化和分泌，随后是基质水肿和蜕膜前反应。直到最近，还不可能同时定量测量表征子宫内膜组织并区分正常功能组织与受疾病影响的组织的数千种人类基因的表达水平。使用GeneChip（R）探针阵列（芯片）技术，我们能够在一次实验中同时测量数千种mRNA的相对浓度。在第一阶段，使用含有大约7200个人类基因的探针的芯片，我们将：1）鉴定在人类月经周期的增殖期在正常子宫内膜中表达的基因。2)鉴定增生期子宫内膜中I-IV期子宫内膜异位症相关基因表达差异。3)使用匹配样本鉴定与子宫内膜异位症II、III和IV期增生性子宫内膜、腹膜病变和卵巢腺瘤相关的表达差异。直到最近，随着用于基因表达监测的寡核苷酸阵列技术的发展，这种范围的项目才变得可行。拟议的商业应用：无可用