2012-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/660216摘要：胚胎著床於母體的子宮內膜是哺乳類動物傳宗接代中不可或缺的步驟，然而，臨床上體外受精（試管嬰兒）療程卻僅能達到約20-30%的胚胎著床率。胚胎著床涵蓋幾個重要步驟，包括對位，附著，穿入，及囊胚侵入子宮內膜。許多細胞生物學機制，包括細胞介白質素，細胞固著分子，免疫細胞之間的交互作用，共同參予了胚胎著床的環境機制。早發性黃體化在體外受精過程中的影響迄今未有定論，它通常定義為血清中的progesterone 濃度在給予HCG 當天（或甚至更早時）有異常上升的情況。早發性黃體化造成不易著床的原因眾說紛紜，有學者認為可能影響卵子品質，但也有學者認為可能造成子宮內膜環境不佳。即便如此，另有學者認為早發性黃體化並不影響體外受精的結果，各種眾說紛紜的說法實乃早發性黃體化造成之病理機制仍不清楚之故。由於利用人類胚胎進行胚胎著床的相關研究有倫理上爭議，因此在本研究中，我們主要將探討早發性黃體化對子宮內膜的效應。本三年期計畫的實驗設計主要包括：第一年： 探討早發性黃體化對胚胎著床的效應，並探討其對子宮內膜細胞的生物效應。第二年： 探討早發性黃體化情況下，對子宮內膜細胞生物效應的分子調控機制。第三年： 主要將以活體模式驗證早發性黃體化對胚胎著床的分子調控機制。我們已經建立了體外探討胚胎著床的細胞實驗模式。人類的Trophoblast細胞株BeWo，被培養成模擬胚胎細胞的細胞團，進一步在內膜細胞上進行各種固著條件測試。我們預期本研究結果將能提供早發性黃體化對內膜組織細胞的分子病理機制，期望藉由對機制的瞭解，能對早發性黃體化的不良反應進行調控，以期未來能提高體外受精療程的胚胎著床率。<br> Abstract: Implantation of the blastocyst into maternal uterus is a crucial step inmammalian reproduction. In the treatment for infertile couples, however, thelow embryo implantation rate (around 20-30%) is a big obstacle that needs tobe overcome. The process of embryo implantation encompasses severaldistinct stages: apposition, adhesion, penetration, and trophoblast invasion.Multiple systems, including cytokines, adhesion molecules, and immune cells,cooperate closely to establish a supportive environment for implantation.Premature luteinization (PL) remains a controversial issue in in vitrofertilization. It is usually defined as subtle, premature increases in serumprogesterone concentrations on or before the day of hCG administration. Theadverse reproductive outcome induced by PL is probably due to either a pooroocyte quality or a detrimental effect on endometrial receptivity. However, itspathogenesis is still poorly understood. Since the employment of humanoocytes is not allowed in the in vitro experiments, the endometrial changesaffected by PL are studied in this project. The research designs of thisthree-year project are as follows. In the first year, the aim is to evaluate theeffect of PL on embryo adhesion and to clarify the major adhesionenhancement molecules. In the second year, the aim is to clarify the molecularmechanism of PL modulated adhesion molecules in endometrial epithelial cells.In the third year, the aim is to verify the mechanism of PL on embryo adhesionin vivo. We start with setting up a model that is available for in vitro evaluationof embryo implantation. Pseudo-embryos are produced from BeWo cells, atrophoblast cell line, and are used to replace the role of human embryos. Thenwe compare the [pseudo-embryo − endometrial glandular cell (EGC)]attachment probabilities after the EGCs are treated with different durations ofmedroxyprogesterone acetate (MPA).We expect the results obtained from this project may provide importantinformation with regard to the pathogenesis of PL, and accordingly will behelpful in enhancing embryo implantation in the future.