HBEGF - A Role In Human Implantation

HBEGF - 在人体植入中的作用

• 批准号: 6620056
• 负责人: RICHARD E LEACH
• 金额: $ 20.12万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620056
• 关键词: antisense nucleic acid; biological signal transduction; cell differentiation; cell proliferation; embryo implantation; endometrium; epidermal growth factor; epithelium; estrogens; gene expression; growth factor receptors; hormone regulation /control mechanism; human tissue; immunocytochemistry; in situ hybridization; in vitro fertilization; messenger RNA; mixed tissue /cell culture; northern blottings; oligonucleotides; phosphorylation; progesterone; protein structure function; receptor expression; trophoblast; western blottings

DESCRIPTION: (Scanned from the applicant's abstract) The steroid-regulated Epidermal Growth Factor (EGF) family and their receptors (HERs) are expressed in the endometrium during implantation in specific spatiotemporal patterns. While there is a well-developed body of knowledge regarding the altered expression of these proteins and adverse effects on implantation in rodents, their expression patterns have not been comprehensively studied in humans during the endometrial cycle and implantation, nor is it known how the hormonal manipulations used during in vitro fertilization (IVF) alter their expression patterns. Our central hypothesis is that the synchronous development of endometrium and invasive trophoblast during early pregnancy is coordinated through the activities of EGF family growth factors, which are expressed in a steroid-dependent, spatiotemporal pattern. Interruption of these signaling pathways by an altered steroid state found during IVF procedures will impact significantly on implantation rates. We will compare the spatiotemporal expression patterns of EGF family growth factors and HER receptor subtypes in endometrial biopsy specimens obtained from women undergoing controlled ovarian hyperstimulation with gonadotropins for the purpose of oocyte donation. We will determine how estrogen and/or progesterone regulate EGF family growth factors and HER gene expression in isolated and co-cultured human uterine epithelial and stromal cells to identify how the Hyperestrogenic State alters this expression. With this information in hand we will determine the effect of candidate EGF family growth factors determined above on specific HER-mediated signaling on trophoblast cell proliferation and invasiveness using in vitro cultured cytotrophoblast cells. Our hypothesis predicts that trophoblast proliferation and differentiation are promoted in a ligand and receptor-specific manner. At the conclusion of this proposed research we will know the effect of hormonal changes found during IVF on EGF family growth factors and their receptors. Further, we will know the effect of this altered expression on trophoblast function. This information will provide mechanistic based strategies to correct the altered endometrial changes associated with IVF treatment. This information in turn can be used in the future to test IVF ovulation induction protocols to improve implantation rates.

描述：（从申请人的摘要扫描）类固醇调节的 表皮生长因子（EGF）家族及其受体（HER）在表皮细胞中表达。 在特定的时空模式中在着床期间的子宫内膜中。 虽然有一个关于改变的知识体系， 这些蛋白质的表达和对啮齿类动物着床的副作用， 它们的表达模式尚未在人类中进行全面研究 在子宫内膜周期和着床期间，也不知道激素是如何影响子宫内膜的。 在体外受精（IVF）过程中使用的操作改变了它们的表达， 模式.我们的中心假设是， 子宫内膜和浸润性滋养细胞在妊娠早期是协调的 EGF家族生长因子的活性，表达于 类固醇依赖性时空模式这些信号的中断 在IVF过程中发现的类固醇状态改变的途径将影响 对着床率影响很大。我们会比较 EGF家族生长因子和HER受体亚型在乳腺癌中的表达模式 从接受控制性卵巢切除术的妇女中获得的子宫内膜活检标本 为了卵母细胞捐赠而用促性腺激素过度刺激。我们将 确定雌激素和/或孕激素如何调节EGF家族生长因子 人子宫内膜上皮细胞中HER基因的表达 和基质细胞，以确定高雌激素状态如何改变这一点， 表情有了这些信息，我们将确定 以上确定的候选EGF家族生长因子对特异性HER介导的 信号转导对滋养层细胞增殖和侵袭力的影响 培养的细胞滋养层细胞。我们的假设是滋养层 在配体中促进增殖和分化， 受体特异性方式。在这项研究的最后，我们将 了解IVF期间发现的激素变化对EGF家族生长的影响 因子及其受体。此外，我们将知道这种改变的效果 滋养层功能的表达。这些信息将提供机械 基于策略来纠正与IVF相关的子宫内膜改变 治疗这些信息反过来可以在未来用于测试IVF 排卵诱导方案，以提高植入率。