HBEGF - A Role In Human Implantation

描述：(摘自申请者的摘要)受类固醇控制的 表皮生长因子家族及其受体(HERs)的表达 在植入过程中子宫内膜中有特定的时空模式。 虽然有关于改变的知识的完善的主体 这些蛋白在啮齿动物体内的表达及其对着床的不良影响， 它们在人类中的表达模式还没有得到全面研究。 在子宫内膜周期和着床期间，也不知道激素是如何 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 妊娠早期子宫内膜与侵袭性滋养细胞的协调 通过EGF家族生长因子的活性，这些生长因子在 类固醇依赖的时空模式。这些信令的中断 在试管受精过程中发现的类固醇状态改变的途径将影响 显著影响着植入率。我们将会比较时空 表皮生长因子家族生长因子及其受体亚型在卵巢癌中的表达 子宫内膜活检标本取自接受控制性卵巢手术的妇女 促性腺激素超刺激用于捐献卵子。我们会 确定雌激素和/或孕激素如何调节EGF家族生长因子 HER基因在分离和共培养的人子宫上皮细胞中的表达 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家族生长因子在特定的HER介导下 滋养层细胞增殖和侵袭信号的体外研究 培养的细胞滋养层细胞。我们的假设预测滋养层细胞 促进增殖和分化的配体和 受体特有的方式。在这项拟议的研究结束时，我们将 了解体外受精过程中发现的激素变化对EGF家庭成长的影响 因子及其受体。此外，我们将知道这一改变的影响 滋养细胞功能的表达。这一信息将提供机械性的 纠正与试管受精相关的子宫内膜改变的基本策略 治疗。这些信息又可以在将来用于试管受精测试 促排卵方案，以提高着床率。

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.