UTERINE LEUKOCYTE REGULATION BY OVARIAN HORMONES

描述：(改编自申请者的摘要)长期工作之一 本实验室的目标是了解子宫的作用 子宫成熟和胚胎着床中的白细胞。的变化 由于病原体的引入、子宫内膜异位症或 自身免疫可改变子宫内膜的募集和激活 白细胞。这些变化可能会对儿童的生育力产生严重影响 受影响的女人。这项建议是为了研究子宫的变化 发生在一组具有自身免疫性的女性中，作为子宫内膜的模型 功能障碍。 白细胞以一种可预测的方式被招募到子宫内膜。 在人类月经的增生期，它们的数量很少。 在分泌中期循环并增加(最佳分泌时间 植入)，伴随着荷尔蒙水平的上升。向下的因素- 调节白细胞功能的细胞也很丰富。 月经周期的分泌期中期表明它们也是 是由类固醇激素引起的。 已有研究表明，患有自身免疫性甲状腺疾病(ATD)的女性 植入率和早孕丢失的增加。中的更改 子宫T细胞数量与子宫内膜细胞因子的变化 与白细胞激活相一致的表达表明，这些女性 可作为子宫内膜失调的模型。因为大多数人 子宫内膜白细胞不表达类固醇激素受体 子宫内膜细胞因子的产生，对卵巢激素的反应， 这与子宫白细胞的募集和激活状态有关。 这项建议将利用子宫内膜间质的体外培养系统 和腺上皮细胞来确定类固醇的反应性是否不同 在患有ATD的女性和对照组之间。半定量逆转法 将进行转录聚合酶链式反应来分析 子宫内膜激素对细胞因子产生的影响 从患有ATD的妇女和对照中分离出的组织。此外，差异 在T细胞中，将使用重定向的细胞毒来确定细胞毒活性 检测，而子宫表达共刺激分子配体需要T 细胞的激活将通过免疫组织化学来确定。通过比较 激素诱导的子宫内膜细胞因子的产生及其激活状态 ATD患者子宫内膜白细胞与对照组的比较 进一步了解白细胞在植入过程中的作用。

DESCRIPTION: (Adapted from applicant's abstract) One of the long term objectives of this laboratory is to understand the role of uterine leukocytes in uterine maturation and embryo implantation. Changes in the uterine environment due to the introduction of pathogens, endometriosis, or autoimmunity can alter the recruitment and activation of the endometrial leukocytes. These changes can have severe consequences on the fertility of the affected woman. This proposal is designed to study the uterine changes that occur in a cohort of women with autoimmunity as a model of endometrial dysfunction. Leukocyte cells are recruited to the endometrium in a predictable fashion. Their numbers are low in the proliferative phase of the human menstrual cycle and increase at mid-secretory phase (the optimal time of implantation), concomitant with rising hormone levels. Factors that down- regulate the functions of the leukocyte cells are also in abundance in the mid-secretory phase of the menstrual cycle suggesting that they are also induced by the steroid hormones. Women with autoimmune thyroid disease (ATD) have been shown to have lower implantation rates and increases in very early pregnancy loss. Changes in both uterine T cell numbers and alterations in endometrial cytokine expression, consistent with leukocyte activation, suggest that these women can serve as a model for endometrial disregulation. Since most of the endometrial leukocyte cells do not express steroid hormone receptors it is the endometrial cytokine production, in response to the ovarian hormones, that is responsible for uterine leukocyte recruitment and activation state. This proposal will utilize an in vitro culture system of endometrial stroma and glandular epithelium to determine if the steroid responsiveness differs between women with ATD and controls. A semi-quantitative reverse transcription polymerase chain reaction will be performed to analyze the cytokine production in response to the steroid hormones from the endometrial tissues isolated from women with ATD and controls. Furthermore, differences in T cell cytotoxic activity will be determined using a redirected cytotoxic assay, while the uterine expression of co-stimulator ligands required for T cell activation will be determined by immunohistochemistry. By comparing hormone induced endometrial cytokine production and the activation state of the endometrial leukocytes in individuals with ATD to controls we hope to gain further insight into the role of leukocytes cells in implantation.