GENE EXPRESSION IN ENDOMETRIOSIS

基因驱动着表征和区分组织类型的生物功能。基因表达的水平和时间控制着细胞的发育、分化、功能和生理。为了更好地了解子宫内膜异位症的病因，我们正在研究未受影响和受子宫内膜异位症影响的妇女的基因表达。子宫内膜异位症是一种影响10%育龄妇女的疾病。正常子宫内膜由增殖性、分泌性和腺性上皮、间质和血管成分组成。上皮细胞以28天为间隔同步增殖、分化和解体。在月经周期的第4-13天，增殖是主要的活动。在增殖期，子宫内膜增厚，以腺上皮内有丝分裂和细胞核假性复层为特征。排卵发生后，分泌期开始(14-28天)，首先是腺上皮细胞的基底液泡化和分泌，然后是间质水肿和蜕膜前反应。直到最近，还不可能同时和定量地测量数千个人类基因的表达水平，这些基因是子宫内膜组织的特征，并区分正常功能组织和受疾病影响的组织。使用基因芯片(R)探针阵列(CHIP)技术，我们能够在一次实验中同时测量数千个mRNAs的相对浓度。在第一阶段，我们将使用包含约7200个人类基因探针的芯片：1)识别在人类月经周期增殖期正常子宫内膜中表达的基因。2)确定增生期子宫内膜I-IV期相关基因表达的差异。3)使用配对样本确定与子宫内膜异位症II、III和IV期增生性子宫内膜、腹膜病变和卵巢子宫内膜异位症相关的表达差异。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，这种规模的项目才变得可行。建议的商业应用：没有可用的

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