MARKERS OF ENDOMETRIAL RECEPTIVITY DURING IMPLANTATION

描述(改编自申请者的描述)：长期目标 这项研究的建议是识别独特的分子标记 人子宫内膜受孕状态的敏感指标 胚胎植入。子宫内膜可以接受发育中的囊胚 仅在有限的时间内植入，称为接受性 在月经周期的阶段。子宫的分子事件 接受性仍不得而知。这项建议的具体目的是：(1) 检测降钙素在人体内的时空表达 月经周期中的子宫内膜。初步研究显示， 调节钙离子的多肽激素降钙素的表达 在人子宫内膜腺上皮中诱导动态平衡 大约在月经周期的分泌中期，但在 增殖期。因为它被认为是 在人类体内的植入在周期的第19-23天之间开始，这些 结果提示降钙素可能是一种潜在的标记物。 植入。为了评估这种可能性，降钙素的概况 将检测月经周期中人子宫内膜的表达 详细采用原位杂交和免疫组织化学方法。(2)至 确定胚胎子宫容受性的其他潜在标志物 植入人体内。信使RNA差异显示(DD) 技术将被用来分离对应于其他 人子宫内膜特异表达的潜在标记基因 在月经周期的分泌中期，推测的时间 植入。这些候选标记物时空表达 基因将在月经周期的子宫内膜中进行检查。(3) 评价子宫容受性的潜在标志物的功能作用 在植入过程中。一种使用反义寡核苷酸的方法 (ODN)是本实验室开发的用于操纵 大鼠子宫中的特异性基因。定向给药反义ODN 针对特定的mRNA，进入植入前阶段的子宫被证明 抑制靶基因表达的稳定水平 植入。阻断一种控制子宫的基因的表达 感受性会影响着床。反义ODN技术在肿瘤治疗中的应用 因此，将使用大鼠模型系统来评估功能 候选标记基因表达减弱的后果 将通过DD技术从人子宫内膜中分离出。

DESCRIPTION (Adapted from Applicant's Description): The long-term objective of this research proposal is to identify molecular markers that are unique and sensitive indicators of the receptive state of human endometrium during embryo implantation. The endometrium can accept a developing blastocyst for implantation only during a limited period of time, termed the receptive phase, during the menstrual cycle. The molecular events underlying uterine receptivity remain unknown. The Specific Aims of this proposal are: (1) To examine the temporal and spatial expression of calcitonin in human endometrium during the menstrual cycle. Preliminary studies show that the expression of calcitonin, a peptide hormone that regulates calcium homeostasis, is induced in the glandular epithelium of human endometrium around the mid-secretory phase of the menstrual cycle but is undetectable in the proliferative phase. Since it is thought that the window of implantation in the human opens between days 19-23 of the cycle, these results suggest that calcitonin may function as a potential marker of implantation. To evaluate this possibility, the profile of calcitonin expression in human endometrium during the menstrual cycle will be examined in detail by in situ hybridization and immunohistochemistry. (2) To identify additional potential markers of uterine receptivity for embryo implantation in the human. Messenger RNA differential display (DD) technique will be used to isolate cDNAs corresponding to additional potential marker genes that are expressed in human endometrium specifically during the mid-secretory phase of the menstrual cycle, the putative time of implantation. The spatio-temporal expression of these candidate marker genes will be examined in the endometrium during the menstrual cycle. (3) To assess the functional roles of potential markers of uterine receptivity during implantation. A method employing antisense oligodeoxynucleotide (ODN) was developed in this laboratory to manipulate the expression of specific genes in rat uterus. Administration of antisense ODN, directed against a specific mRNA, into the preimplantation phase uterus was shown to suppress the steady-state level of the targeted mRNA around the time of implantation. Blockade of expression of a gene that controls uterine receptivity would impair implantation. The antisense ODN approach in the rat model system will therefore be used to evaluate the functional consequence of the attenuation of expression of candidate marker genes that will be isolated from human endometrium by the DD technique.