CHEMOATTRACTIONS IN REPRODUCTIVE TISSUES

生殖组织中的化学吸引力

• 批准号: 2194583
• 负责人: AYDIN M ARICI
• 金额: $ 8.45万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2194583
• 关键词: antisense nucleic acid; cell adhesion molecules; cell migration; chemoattractants; chemotaxis; enzyme linked immunosorbent assay; female; gene expression; growth factor; hormone regulation /control mechanism; human subject; immunocytochemistry; in situ hybridization; interleukin 8; laboratory rat; leukocyte activation /transformation; macrophage; messenger RNA; monocyte; neutrophil; northern blottings; ovary; progesterone; tissue /cell culture; uterus

Macrophages and granulocytes are present in reproductive tissues where they participate in and affect many aspects of ovarian and u tetrine function. The hypothesis to be tested in this proposal is that leukocyte migration in the ovaries is hormonally regulated and this regulation occurs through modulation of chemotactic factors. Based on the applicant's preliminary results the focus of this research will be study the physiologic relevance of chemotactic factors for the recruitment and activation of macrophages and neutrophils in the ovary. Regulation of the traffic of leukocytes by chemoattractant, such as interleukin-8 that acts on neutrophils and monocyte chemotactic protein-1 that acts on monocyte/macrophages, followed by the secretion of specific paracrine factors by the leukocytes may be one of the ways by which certain reproductive events such as ovulation and luteal function are controlled. Based on our hypothesis, the long-range goal of this research is to define bimolecular events modulating the expression of these factors in humans. To accomplish this goal and to provide optimal opportunity for the applicant to perfect the investigative skills necessary for independent research, we propose three specific aims as follows: Specific Aim 1. To identify and characterize the functional significance of specific chemotactic factors (IL-8 and MCP-1) in reproductive physiology using a rodent model. Specific Aim 2. To identify and characterize in humans the presence and variations of the expression of these chemoattractant (IL-8 and MCP-1) in the ovaries throughout the menstrual cycle and during pregnancy. Specific Aim 3. To investigate the in vitro regulation of the expression of these chemoattractant by gonadal steroid hormones, growth factors and cytokines. A definition of the bimolecular events related to chemoattraction of migratory cells relevant to ovulation and luteal function will be important in advancing our understanding of these aspects of reproductive biology. We believe that series of focused investigations that explore the physiologic relevance of the chemoattractant factors in regulating the chemotaxis and activation of macrophages and neutrophils in reproductive tissues may reveal new insights into the etiology of ovulatory dysfunctions, infertility and early pregnancy losses.

巨噬细胞和粒细胞存在于生殖组织中， 它们参与并影响卵巢和子宫内膜的许多方面， 功能 本提案中要检验的假设是， 卵巢中的迁移受生殖调节， 通过调节趋化因子发生。 基于 申请人的初步结果，本研究的重点将是研究 趋化因子与募集的生理相关性， 卵巢中巨噬细胞和中性粒细胞的活化。 调控 白细胞通过化学引诱物的运输，如白细胞介素-8， 作用于中性粒细胞和单核细胞趋化蛋白-1， 单核细胞/巨噬细胞，随后分泌特异性旁分泌 白细胞的因子可能是某些 控制诸如排卵和黄体功能的生殖事件。 根据我们的假设，这项研究的长期目标是 定义调节这些因子表达的双分子事件， 人类 为了实现这一目标，并提供最佳机会， 申请人完善必要的调查技能， 独立研究，我们提出了三个具体目标如下：具体 目标1. 识别和描述的功能意义 生殖生理学中特异性趋化因子（IL-8和MCP-1） 使用啮齿动物模型。 具体目标2。 识别和描述 人类的存在和这些表达的变化 在整个月经期间卵巢中的化学引诱物（IL-8和MCP-1） 周期和怀孕期间。 具体目标3。 为了研究体外 性腺激素对这些化学引诱物表达的调节 激素、生长因子和细胞因子。 双分子的定义 与迁移细胞的化学吸引相关的事件 排卵和黄体功能将是重要的， 了解生殖生物学的这些方面。 我们认为 一系列有针对性的调查，探索生理相关性 趋化因子在调节趋化性中的作用， 生殖组织中巨噬细胞和中性粒细胞的激活可能 揭示了排卵功能障碍病因学的新见解， 不孕症和早孕丢失。