UTERINE LEUKOCYTE REGULATION BY OVARIAN HORMONES

描述：（改编自申请人的摘要）长期 本实验室的目的是了解子宫的作用， 白细胞在子宫成熟和胚胎着床中的作用。 变化 由于引入病原体、子宫内膜异位症或 自身免疫可以改变子宫内膜的募集和激活， 白细胞 这些变化可能对生育率产生严重影响。 受影响的女人 本建议旨在研究子宫的变化 这发生在一群自身免疫性妇女中，作为子宫内膜异位症的模型， 功能障碍 白细胞以可预测的方式被募集到子宫内膜。 它们的数量在人类月经的增殖期很低 周期和增加在中期分泌期（最佳时间， 植入），伴随着激素水平的升高。 降低的因素- 调节白细胞功能的蛋白质也大量存在于 月经周期的中期分泌期，这表明它们也是 由类固醇激素引起的 患有自身免疫性甲状腺疾病（ATD）的女性已被证明具有较低的 植入率和极早期妊娠丢失的增加。 变化 子宫T细胞数量和子宫内膜细胞因子的变化 表达，与白细胞活化一致，表明这些妇女 可以作为子宫内膜失调的模型。 由于大部分 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， 其负责子宫白细胞募集和活化状态。 本研究将利用子宫内膜基质的体外培养系统 和腺上皮，以确定类固醇反应是否不同， ATD患者和对照组之间的差异 半定量的逆转 将进行转录聚合酶链反应以分析 子宫内膜对类固醇激素反应的细胞因子产生 从患有ATD的女性和对照组中分离的组织。 此外，差异 在T细胞中的细胞毒活性将使用重定向的细胞毒性测定试剂盒测定。 检测，而T细胞所需的共刺激配体的子宫表达 通过免疫组织化学测定细胞活化。 通过比较 激素诱导的子宫内膜细胞因子的产生和 ATD患者的子宫内膜白细胞与对照组相比， 进一步了解白细胞在植入中的作用。

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.