人類濾泡期、黃體期、正常懷孕、不正常懷孕及反覆性流產之子宮內膜及蛻膜中巨噬細胞(M1/M2亞型比例)之分析

Macrophages (M1/M2 ratio) in the endometrium at follicular and secretory phases and deciduae from normal, abnormal pregnancies and recurrent spontaneous abortions in human

曹芳瑜(Fang-Yu Tsao)

指導教授 ： 何弘能

國立臺灣大學/醫學院/免疫學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.02331

摘要

在哺乳類中，胎兒因為帶有一半來自父系的基因而被視為是一半異體移植物(semi-allogeneic graft)。在正常情況下，胎兒能在子宮內正常生長而不被母體免疫系統排斥。因此，免疫細胞被認為在受精卵著床時的環境中扮演重要角色，不僅能維持母親正常免疫功能以對抗外界病原，還能夠產生適當的免疫調適。子宮蛻膜中數量第二多的巨噬細胞(20~25%)在此調適中可能扮演重要的角色，也是本實驗主要探討的對象。一直以來，巨噬細胞被認為會根據不同的刺激及所處的環境，特別是受到懷孕初期性荷爾蒙的影響，而極化成M1及M2兩種類型，且此兩種類型細胞比例的不平衡是否可能導致流產有待進一步探討。臨床上，有些婦女受不明原因的反覆性流產所苦，且給予標準的治療方法也未見起色。因此，我們利用免疫組織螢光染色的方法探討這兩群細胞的比例在受到賀爾蒙波動的影響下:在不同月經週期、正常、不正常懷孕及反覆性流產的情況下有何差異，試圖找尋造成不明原因流產可能的病理及生理原因。實驗結果顯示，在不正常懷孕及反覆性流產的情形下，M1細胞的比例較高；而處於黃體期或正常懷孕的婦女則擁有較高比例的M2細胞。此結果意味著M2細胞在準備懷孕及支持正常懷孕的情況中扮演重要的角色；過多的M1巨噬細胞可能藉由引發過多的發炎反應而導致不正常的懷孕或反覆性流產。了解M1/ M2的分布比例及可能的病理及生理原因，未來將有助於治療方法的開發及幫助預測不明原因流產婦女的懷孕結果。

關鍵字

M1/M2巨噬細胞 ； 蛻膜巨噬細胞 ； 母體免疫調適 ； 反覆性流產

並列摘要

In mammals, the developing embryo-placenta unit is considered as a semi-allogeneic graft. Maternal immunomodulation allows the acceptance and growth of the fetus without being rejected in the uterus. Immune cells in decidua, holding a key role during the implantation, not merely keep maternal immunomodulation but also maintain defense of host and fetus against pathogens. Decidual macrophages represent the second largest proportion of leukocyte in the uterus so their roles in maintaining maternal tolerance shall not be overlooked and are the main target cells in this study. Macrophages might be polarized to M1 or M2 subpopulations by the stimulation from uterine microenvironment, especially those hormones and cytokines during implantation in early pregnancy. The imbalance of M1/M2 might link to pathological pregnancies. Clinically, some women, healthy but refractory to traditional therapies, suffered from unexplained recurrent spontaneous abortions without defined etiologies. Hence, our goal is to evaluate the M1/M2 ratio in vivo the condition of hormone fluctuation during different menstrual phases and various groups of women with normal and abnormal pregnancies and recurrent spontaneous abortions with immunofluorescence studies to find out the possible pathophysiology of abortions. The results demonstrated that M1 macrophages are abundant in abnormal pregnancies and RSA and the frequency of M2 macrophages is significantly higher in luteal phase and normal pregnancies. It suggested that M2 macrophage may be the imperative role in preparing for and upholding pregnancy and that high level of M1 macrophages may induce spontaneous abortions due to promoting excessive inflammation. This study may provide directions for developing new treatment and the level of M1/M2 in the future might be the predictor of pregnancy outcome in women with unexplained abortion.

並列關鍵字

M1/M2 Macrophages ； decidual macrophages ； maternal immunomodulation ； recurrent spontaneous abortion

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