子宫内膜单胺氧化酶A（MAO-A）在反复IVF-ET失败患者种植窗口期的表达及其意义

目的：探讨子宫内膜单胺氧化酶A（MAO—A）在评估子宫内膜容受性中的作用。方法：应用实时荧光定量PCR和免疫组织化学技术,检测3次IvF-ET失败患者fA组,n=39）、2次IVF-ET失败,第3次获得临床妊娠患者（B组,行=8）、首次IVF—ET获得临床妊娠患者（C组,n=21）在子宫内膜种植窗口期子宫内膜MAO-AmRNA的表达和MAO-A蛋白的表达及定位,同时扫描电子显微镜观察子宫内膜的胞饮突数量及发育情况,探讨子宫内膜MAO—A在评估子宫内膜容受性中的作用。结果：反复IVF-ET失败患者在子宫内膜种植窗口期子宫内膜MAO-A的表达低于首次IvF-ET获得临床妊娠的患者（P〈0．05）。结论：子宫内膜MAO-A可以作为子宫内膜容受性的预测指标。     

PCOS患者子宫内膜白血病抑制因子的表达及意义

目的:探讨多囊卵巢综合征(PCOS)患者不同组织学分期的子宫内膜白血病抑制因子(LIF)的表达与子宫内膜容受性的关系。方法:20例已婚PCOS患者(PCOS组)和26例已婚不孕症患者(对照组)在月经周期第5￣14日及排卵后7￣8 d采集其子宫内膜标本,经HE染色判定内膜组织学分期,采用免疫组织化学法检测内膜LIF的表达。结果:PCOS组间质反应不良和分泌反应欠佳的发生率均高于对照组,差异有统计学意义(χ2=5.000,P<0.05;χ2=7.219,P<0.01)。LIF的表达以腺上皮细胞的胞质为主,其在分泌中期子宫内膜的表达水平均高于增生期(P<0.01)。LIF在PCOS组增生期和分泌中期子宫内膜的表达水平均低于其相应的对照组(P<0.01)。结论:PCOS患者着床窗口期LIF的低表达可能影响着床的多个环节,参与了PCOS患者内分泌紊乱纠正后仍出现妊娠率低、流产率高的发生、发展过程。     

细胞凋亡调控蛋白bcl-2和bax在多囊卵巢综合征患者子宫内膜中的表达

目的探讨多囊卵巢综合征（PCOS）患者子宫内膜中细胞凋亡调控蛋白bcl-2和bax的表达及其在PCOS患者子宫内膜病变中的意义。方法应用免疫组织化学SP方法,测定18例PCOS患者子宫内膜和27例月经周期正常、因输卵管不通或男性不育就诊的对照者子宫内膜（10例增殖期、17例分泌期）bcl-2和bax蛋白的表达。结果PCOS患者子宫内膜bcl-2表达较对照者增殖期和分泌期高（P＜0．05和P＜0．01）,但bax表达相似（p＞0．05）。结论PCOS患者子宫内膜bcl-2蛋白表达增高,与bax形成更多的异源二聚体,从而抑制PCOS子宫内膜凋亡,对其子宫内膜的异常增生改变起一定作用。     

IGF—I和Bcl-2蛋白在多囊卵巢综合征胰岛素抵抗患者子宫内膜中的表达

目的通过对子宫内膜中胰岛素样生长因子-I（insulin—like growth factor—I,IGF—I）和Bcl-2基因蛋白表达的研究,探讨多囊卵巢综合征（PCOS）患者胰岛素抵抗对子宫内膜增生的作用机制。方法采用免疫组织化学ABC法检测92例PCOS胰岛素抵抗患者子宫内膜中IGF-1及Bcl-2的表达。结果PCOS体胰岛素抵抗患者子宫内膜中IGF-I表达量（203．54±18．29）较非胰岛素抵抗组的表达量（187．22±15．46）明显升高,差异有统计学意义（P〈O．001）;胰岛素抵抗组Bcl-2的表达量（200．94±15．43）与非胰岛素抵抗组（188．69±18．72）比较,差异有统计学意义（P〈O．01）;IGF—I与Bcl-2在子宫内膜中的表达呈正相关关系（r=0．42,P〈0．001）。结论PCOS胰岛素抵抗患者子宫内膜增生的发病可能与IGF—I及Bcl-2蛋白的表达有关。     

自然及促排卵周期子宫内膜整合素α4β1的表达

目的 了解氯米芬（CC）、绝经期促性腺激素（hMG）对黄体中期子宫内膜整合素α4β1表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术检测48例正常妇女自然周期以及48例正常妇女、30例多囊卵巢综合征患者应用CC／绒毛膜促性腺激素（hCG）及CC／hMG/hCG方案促卵治疗后黄体中期子宫内膜整合素α4β1的表达。结果 子宫内膜整合素α4β1在正常妇女自然周期着床窗口期呈现强阳性表达,而CC、hMG抑制整合率α4β1的表达,两者比较,差异有极显著性（P＜0．01）;妊娠者较妊娠者整合素α4β1表达强度高。结论 促排卵周期黄体中期整合素α4β1表达下降或缺失,子宫内膜容受性下降,妊娠率降低。     

不明原因不孕患者子宫内膜种植窗口期整合素αvβ3与基质金属蛋白酶9的表达及其相关性研究

不明原因不孕的发病机理尚未完全清楚。近年来发现，子宫内膜局部调节失衡，导致子宫内膜容受性下降，可能是不明原因不孕的病因之一。本研究通过测定子宫内膜种植窗口期整合素αvβ3、基质金属蛋白酶9(MMP-9)的表达，并比较两者的相互关系，旨在为将MMP-9、整合素αvβ3确定为子宫内膜容受性标志物提供实验依据。     

子宫内膜MMP-3表达和子宫腺肌病痛经的关系研究

目的研究基质金属蛋白酶（MMP～3）在子宫腺肌病中的表达,探讨其表达与子宫腺肌病的发生及痛经的相关性。方法应用免疫组化PV6000法检测45例子宫腺肌病在位内膜,36例异位内膜及28例对照组子宫内膜MMP-3的表达。结果MMP-3在子宫腺肌病异位内膜组中的表达显著高于子宫腺肌病在位内膜组及对照组（P〈O．05）。MMP-3在子宫腺肌病在位内膜增殖期和分泌期的表达强度比较,差异无统计学意义（P〉O．05）。MMP-3在子宫腺肌病异位内膜组中的表达与子宫腺肌病患者痛经呈正相关（r=O．557,P〈0．05）。结论MMP-3的异常表达可能与子宫腺肌病及其痛经的发生有关。     

凋亡调节基因Bcl-2,Bax在汉族和维族妇女子宫内膜异位症表达的对比研究

目的 检测凋亡调节基因蛋白Bcl-2，Bax在汉族和维吾尔族（维族）妇女子宫内膜异位症（EMs）中的表达，以探讨凋亡调节基因在子宫内膜异位症发病中的作用。方法 2004年11月～2006年1月，新疆医科大学第一附属医院应用免疫组化法，检测凋亡调节基因蛋白Bcl-2、Bax在无FAts妇女的正常子宫内膜与卵巢EMs患者异位、在位内膜中的表达。结果 Bcl-2、Bax主要定位于子宫内膜的腺上皮：①维、汉族对照组子宫内膜增生期Bcl-2的表达高于分泌期（P〈0．05），Bcl-2在EMs患者异位、在位内膜中的表达较无EMs者增强，差异有显著性意义（P〈0．05）；②Bax在维、汉族对照组子宫内膜增生期和分泌期都强表达，差异无显著性（P〉0．05）。在EMs患者，在位及异位内膜中表达比对照组子宫内膜低，差异有显著性（P〈0．05）。结论 卵巢EMs中凋亡调节基因的表达与无EMs者不同，促凋亡基因的表达减弱，抑制凋亡基因的表达增强，有利于异位内膜的种植生存和发展、凋亡基因蛋白Bcl-2与Bax在维族和汉族卵巢EMs的表达差异无显著性（P〉0．06）。     

卵巢早衰患者激素替代周期子宫内膜微创术的应用

目的探讨子宫内膜微创术改善卵巢早衰患者子宫内膜容受性的过程中的作用。方法研究组:选择中国人民解放军海军总医院妇产科生殖中心2007年1~10月行供卵体外受精(IVF)失败3次以上的卵巢早衰患者3例,第1周期在胚胎移植前激素替代周期第21天(种植窗口期)行子宫内膜活检,分别于第2和第3个激素替代周期的第10天行子宫内膜微创术,同期取内膜,SEM下观察子宫内膜的超微结构,选择合适的周期进行供胚移植。对照组:选择同期正常月经周期妇女10例,观察其种植窗口期子宫内膜胞饮突的发育情况。结果对照组:SEM低倍镜下分泌期子宫内膜胞饮突发育良好,且表达丰富。研究组:微创术前,SEM下子宫内膜上皮细胞排列紊乱,细胞比例失衡,没有发现胞饮突,部分细胞呈凋亡状;第1次微创术后,SEM下子宫内膜上皮细胞排列整齐,依稀可见胞饮突,凋亡情况已明显改观;第2次微创术后,SEM下子宫内膜上皮细胞排列整齐,可见较多胞饮突,无凋亡表现,与对照组无显著差异。研究组3例患者均于2次微创术后次月再次同法行微创术,当月于种植窗口期行胚胎移植术,随访得知3例均于移植后获得临床妊娠。结论子宫内膜微创术可以改善卵巢早衰患者子宫内膜容受性;胞饮突可用于评价子宫内膜容受性。     

IL-10在子宫腺肌病种植窗期在位内膜的表达与子宫腺肌病内膜容受性的关系

目的：分析IL-10在子宫腺肌病患者在位内膜种植窗期的表达,探讨子宫腺肌病患者内膜容受性下降的免疫学因素。方法：分别取子宫腺肌病、非腺肌病患者在自然周期种植窗期的内膜组织。子宫腺肌病患者18例,对照组16例,采用免疫组化SP法检测内膜组织中IL-10的表达。结果：IL-10在腺肌病患者内膜腺体和间质的表达较非腺肌病患者减弱（P〈0．05）,差异有统计学意义。结论：子宫腺肌病患者在位内膜中具有妊娠保护作用的IL-10表达减低,推测IL-10的表达降低是导致子宫腺肌病患者内膜容受性下降的免疫学因素。     

Microarray evaluation of endometrial receptivity in Chinese women with polycystic ovary syndrome

Patients with polycystic ovary syndrome (PCOS) have lower pregnancy and higher miscarriage rates, possibly due to decreased endometrial receptivity. In this study, endometrium was processed for RNA extraction and hybridization of chemically fragmented, biotinylated, complementary RNA on high-density oligonucleotide microarrays, and screened for 21,571 genes. Real-time polymerase chain reaction (PCR) was used to verify the result. Genes found to be down-regulated in the endometrium during the implantation window in PCOS patients included those whose activity was integral to membrane function, adhesion, invasive growth and the cytoskeleton. Among these genes, some have previously been associated with endometrial receptivity (by microarray research or other methods) and some have never previously been associated with endometrial receptivity. Using real-time PCR, expression of transmembrane 4 superfamily member 4 (TM4SF4) and matrix metalloproteinase 26 (MMP26) was found to be significantly decreased during the implantation window in patients with PCOS (P= 0.003). TM4SF4 has been demonstrated to be associated with adhesion; MMP26 has been shown to be related to degradation of extracellular matrix. It is suggested the down-regulated gene expression during the implantation window in patients with PCOS indicates differential gene expression in the endometrium between PCOS and normal women during the implantation window. This might affect endometrial receptivity.     

促排卵周期PCOS妇女子宫内膜纤维粘连蛋白及层粘连蛋白的表达

目的:了解促排卵药物氯米酚(CC)、hMG及GnRH-a对黄体中期子宫内膜内膜纤维粘连 蛋白(FN)及层粘连蛋白(LN)表达的影响。方法:应用单克隆抗体,采用免疫组织化学技术检测50 例正常妇女自然周期以及50例正常妇女,45例多囊卵巢综合征妇女应用CC／hCG,CC／hMG／hCG 及GnRH-a／hMG／hCG方案促排卵治疗后黄体中期子宫内膜FN和LN的表达。结果:子宫内膜FN 和LN表达在正常妇女自然周期着床窗口时呈现强阳性;而CC、hMG抑制FN和LN的表达,使 其阳性强度减弱,有显著性统计学差异P<0．01;GnRH-a对FN和LN抑制不明显。同时妊娠者较 未妊娠者FN和LN表达强度高。结论:CC／hCG及CC／hMG／hCG方案促排卵后黄体中期子宫内膜 中FN和LN表达下降或缺失,内膜容受性下降,妊娠率降低。     

Endometrial Pinopode and αvβ3 Integrin Expression Is Not Impaired in Infertile Patients with Endometriosis

PURPOSE: To investigate endometrial receptivity in terms of pinopode formation and alphavbeta3 integrin expression in infertile women with endometriosis during natural cycles. METHODS: We investigated the expression of alphavbeta3 integrin and pinopode formation in the endometrium of 12 infertile patients with stage I or II endometriosis as the only cause of infertility, 12 infertile patients having unexplained infertility, and 12 fertile women who were undergoing tubal sterilization. Two endometrial biopsies (postovulatory day +7 to +8 and 4 days later) were performed during a single menstrual cycle in each subject. RESULTS: No statistically significant difference regarding alphavbeta3 integrin expression and pinopode formation was found between infertile patients with endometriosis and the two control groups. CONCLUSION: alphavbeta3 integrin expression and pinopode formation are not reduced during the window of implantation in patients with stage I-II endometriosis. Whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with those markers of implantation, warrants further studies.     

氧化应激对子宫内膜异位症患者在位内膜容受性的影响

目的:探讨氧化应激(OS)对子宫内膜异位症(EMs)患者在位内膜容受性的影响。方法:采用黄嘌呤氧化酶法及硫代巴比妥酸比色法分别检测60例EMs患者(EMs组)在位内膜(增殖期24例,分泌期36例)和50例正常内膜(对照组)(增殖期21例,分泌期29例)中超氧化物歧化酶(SOD)和丙二醛(MDA)水平。采用同种方法检测对照组内种植窗期内膜17例(A组),EMs组经治疗后口服维生素C(Vc)抗氧化治疗患者恢复正常月经后第1个月种植窗期内膜12例(B组),EMs组经治疗后患者恢复正常月经后第1个月种植窗期内膜11例(C组)和EMs组内种植窗期内膜23例(D组)中SOD和MDA水平。采用免疫组化法检测A、B、C、D组内膜整合素αvβ3表达情况。分析A、B、C、D组内膜整合素αvβ3表达与SOD、MDA水平相关性。结果:无论增殖期还是分泌期内膜,EMs组的SOD水平均低于对照组(P0.05),MDA水平均高于对照组(P0.05)。4组种植窗期内膜中,SOD水平为A组B组C组D组,MDA水平为A组B组C组D组,αvβ3水平为A组B组C组D组;B、C、D组中,内膜整合素αvβ3表达与SOD水平均呈正相关(P0.05),与MDA水平均呈负相关(P0.05)。结论:EMs患者在位内膜存在OS,其降低在位内膜容受性;治疗后的EMs患者可明显改善在位内膜OS状态,进而改善在位内膜容受性,抗氧化治疗可以起到辅助作用。     

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-3 mRNA expression in ectopic and eutopic endometrium in women with endometriosis: a rationale for endometriotic invasiveness

OBJECTIVE: To investigate mRNA expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-3 (TIMP-3) in ectopic endometriosis tissue and uterine endometrium from women with and without endometriosis throughout the menstrual cycle. DESIGN: Molecular studies in human tissue. SETTING: Department of Gynecology and Obstetrics, Reproductive Immunology Laboratory, Stanford University Medical Center. PATIENT(S): Fifty-three premenopausal woman (23 women with endometriosis and 30 women without endometriosis undergoing laparoscopic surgery). Endometrium and ectopic endometriosis tissue were obtained at the time of surgery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): mRNA expression from eutopic and ectopic endometrium was analyzed by quantitative, competitive PCR. RESULT(S): Both uterine endometrium and ectopic endometriotic tissue from women with endometriosis expressed significantly (P<.05) lower levels of TIMP-3 than endometrium from normal women. Also, ectopic endometrium expressed higher levels of MMP-9 and a higher ratio of MMP-9/TIMP-3 than eutopic endometrium from normal and endometriosis patients. CONCLUSION(S): These results suggest that ectopic and eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater MMP and less TIMP-3 mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one of the reasons for the invasive properties of the endometrium, resulting in the development of endometriosis.     

The expression of integrin beta 3 in cycling and early pregnant endometrium and its relationship with primary unexplained infertility

OBJECTIVES: To profile the changes in integrin beta 3 expression in cycling and early pregnant endometrium and its relationship with unexplained infertility. METHOD: Expression of integrin beta 3 on endometrium was detected in 56 normal cycling women during different menstrual phases or early pregnant women, and 9 cases with unexplained infertility during mid-luteal phase by immunohistochemistry technique. RESULTS: Integrin beta 3 was expressed only in the midluteal or pregnant endometrium(after cycle day 19). Compared with normal women, integrin beta 3 failed to express in the midluteal endometrium from women with unexplained infertility. CONCLUSIONS: Our findings suggest integrin beta 3 may play important roles in the process of implantation and decidualization. It might be a new reliable marker of uterine receptivity. Abnormal endometrial integrin beta 3 expression might be the major cause of unexplained infertility.     

不明原因不孕患者着床窗期子宫内膜形态结构与性激素及其受体表达

目的:研究着床窗期子宫内膜形态结构与性激素及其受体表达判断不明原因不孕患者的子宫内膜条件及黄体功能。方法:活检不明原因不孕55例及正常生育16例着床窗期子宫内膜行组织学天数及组织学分型;内膜扫描电镜观察胞饮突。检测黄体功能缺陷8例及子宫内膜反应不良6例着床窗期内膜性激素及其受体。结果:不孕组内膜的发育同步率(63.6%)明显低于正常生育组(93.8%),差异有统计学意义(P<0.05)。不孕组子宫内膜胞饮突数量少,且发育明显滞后于正常生育组。黄体功能缺陷患者着床窗期子宫内膜孕激素受体表达与正常生育组无统计学差异(P>0.05);子宫内膜反应不良患者孕激素受体表达明显低于正常生育组,差异有统计学意义(P<0.05)。结论:着床窗期子宫内膜发育同步性差,内膜容受性欠佳可能是部分不明原因不孕的病因之一。鉴别由黄体功能缺陷抑或子宫内膜反应不良引起的分泌期子宫内膜发育不良,是临床选择治疗方案的关键。     

Is glycodelin an important marker of endometrial receptivity?

OBJECTIVE: Glycodelin A (GdA) is viewed as a uterine endometrium receptivity marker. The expression of GdA in the endometrium is mirrored in uterine fluid and in the serum. Thanks to its immunosuppressive properties GdA might regulate mechanisms of fertilization, implantation and further development of the embryo. DESIGN: The authors assessed the GdA concentration during implantation window of nonconceptional cycles in women with impaired reproduction. MATERIAL AND METHODS: Fluid from uterine cavity, serum and endometrial samples were obtained from 116 women, among them 43 have had 2 or more miscarriages, while 52 were infertile. Control constituted 21 fertile women. In uterine fluid and serum the GdA concentration was assessed with ELISA Bioserv Diagnostic kits, and progesterone with electrochemiluminescence. Endometria obtained during hysteroscopy were evaluated in terms of conformity with the cycle dating. RESULTS: Statistically lower (p < 0,0001) compared to control GdA concentration in uterine fluid was found in infertile women. The lowest GdA values were obtained in women with idiopathic infertility and infertile women with endometriosis. GdA level of women with 2 or more miscarriages was no statistically significant different compared to control. The lowest concentration of GdA in this group of patients was found in women with luteal phase deficiency. The GdA concentration in the serum was three times lower compared to values noted in uterine fluid, and there was no difference between studied groups. CONCLUSION: Based on our research we might conclude that GdA has a more important role during implantation than in further development of the embryo.