子宫内膜容受性相关调控因子的时序表达及功能

胚胎着床是复杂的程序化的生理过程。子宫内膜仅在极短时期内允许胚泡植入,此时子宫内膜达到最大胚泡种植容受性。子宫内膜容受性形成过程中受多种细胞因子、蛋白分子调控,这些特定调控因子在子宫内膜发育分化过程中呈现较为显著的时空表达特征,对内膜容受性形成有重要作用。相关细胞因子(白血病抑制因子、白细胞介素)、蛋白分子(胎盘蛋白、半乳糖凝集素-1)及特定转录因子(同源框基因)在子宫内膜容受性形成过程中伴随短暂、瞬间性高表达,其表达量为增生期的4～5倍,该时期与着床窗期时间一致,呈现出时空特异性。表明这几类生物活性分子可能与子宫内膜容受性形成密切相关。     

子宫内膜容受性相关调控因子的时序表达及功能

胚胎着床是复杂的程序化的生理过程.子宫内膜仅在极短时期内允许胚泡植入,此时子宫内膜达到最大胚泡种植容受性.子宫内膜容受性形成过程中受多种细胞因子、蛋白分子调控,这些特定调控因子在子宫内膜发育分化过程中呈现较为显著的时空表达特征,对内膜容受性形成有重要作用.相关细胞因子(白血病抑制因子、白细胞介素)、蛋白分子(胎盘蛋白、半乳糖凝集素-1)及特定转录因子(同源框基因)在子宫内膜容受性形成过程中伴随短暂、瞬间性高表达,其表达量为增生期的4～5倍,该时期与着床窗期时间一致,呈现出时空特异性.表明这几类生物活性分子可能与子宫内膜容受性形成密切相关.     

薄型子宫内膜的临床处理进展

有着床能力的胚胎、容受性良好的子宫内膜以及胚胎和母体的相互作用是胚胎成功种植的主要因素。子宫内膜厚度仍是目前临床评价子宫内膜容受性的重要指标。月经周期中子宫内膜厚度可以反映内膜功能状态,子宫内膜充分的增殖和向分泌期转化是胚胎成功着床的前提条件之一。目前一致认为,薄型子宫内膜显著降低胚胎种植率,此外,薄型子宫内膜也是导致女性不孕的重要原因之一。因此,探索薄型子宫内膜的病因并积极治疗、提高子宫内膜的容受性非常重要。对妨碍胚胎种植的子宫内膜进行预处理,通过治疗使子宫内膜增加至正常厚度,将有助于提高妊娠率及活产率。然而,目前薄型子宫内膜的治疗方法大多效果不理想。综述薄型子宫内膜的定义、病因及临床处理研究进展。     

经阴道超声评价IVF周期患者子宫内膜容受性的价值

子宫内膜容受性(ER)是决定体外受精-胚胎移植(IVF-ET)是否成功的关键因素之一。经阴道超声作为一种无创、可重复检查的手段,在辅助生育技术方面有其特有的优势。本文综述了近年来国内外学者利用经阴道超声从子宫内膜厚度、形态、内膜容积以及内膜和内膜下血流等方面评价子宫内膜容受性的价值。     

子宫内膜容受性的评价指标及其应用价值

现代辅助生殖技术(ART)中,子宫内膜容受性受损成为限制胚胎成功种植的重要因素之一。如何合理评价子宫内膜容受性一直是临床和基础研究关心的问题。本文主要综述目前用于评估子宫内膜容受性的临床指标,形态学、分子标志物,以及最新的蛋白组学评估方法,并分析其应用价值,以期提供更好、更客观和实时的子宫内膜容受性的评价指标,进而更加有的放矢地治疗不孕症患者,最大可能提高ART妊娠率。     

子宫内膜容受性的研究进展

子宫内膜容受性是胚胎植入的关键因素,作为生育的必要条件一直备受关注。改善子宫内膜容受性将显著提高临床妊娠率。近年来,国内外对于子宫内膜容受性的研究从未间断,发现众多与子宫内膜容受性相关的生物分子,如有关基因、蛋白、细胞因子、微小RNA、子宫内膜菌群都影响着子宫内膜容受性的建立,但有关子宫内膜容受性的临床应用研究还较少,尚待进一步完善。总结分析子宫内膜相关因子对子宫内膜容受性的作用研究文献,以期为临床工作者对子宫内膜容受性的评估及改善治疗带来一定的帮助。     

基质金属蛋白酶-9及其抑制物-3在人种植窗期子宫内膜的表达特点及作用

目的　探讨基质金属蛋白酶 9(MMP 9)和组织金属蛋白酶抑制物 3(TIMP 3)蛋白在人种植窗期子宫内膜组织中表达的特点 ,及其在胚胎着床中的作用。方法　应用链菌生物素蛋白 过氧化酶连接法 ,观察 13例增殖期、10例分泌早期、17例种植窗期及 15例分泌晚期子宫内膜组织中MMP 9和TIMP 3蛋白的表达特点及其阳性细胞的分布规律。结果　MMP 9和TIMP 3蛋白在各期子宫内膜中均有表达 ,从增殖期到分泌早期至种植窗期 ,MMP 9和TIMP 3蛋白染色逐渐增强 ,以种植窗期增强最为明显 ,分泌晚期染色强度虽较种植窗期略低 ,但仍明显高于增殖期。结论　种植窗期子宫内膜中MMP 9和TIMP 3蛋白为高表达 ,可能参与胚胎着床的调节 ,有利于胎盘的形成     

子宫内膜容受性的调控及其特征标记的研究进展

胚泡着床是一复杂的生理过程。着床只发生在具有接受性的子宫内膜,子宫对胚泡的接受性叫容受性。子宫内膜容受性的调控机制尚不清楚,涉及卵巢甾体激素,细胞因子和黏附分子等的自分泌及旁分泌机制。综述子宫内膜容受性的调节机制及特征性标记。     

人子宫内膜容受性相关基因的研究进展

良好的子宫内膜容受性是胚胎着床成功的关键因素,近年来通过基因芯片技术展开了对子宫内膜容受性相关基因的高通量筛选研究。学者们通过对正常妇女正常月经周期子宫内膜基因表达差异的研究,初步总结出一些与子宫内膜容受性相关的基因,同时也发现子宫内膜异位症及不明原因不孕的妇女子宫内膜基因表达异于正常妇女,某些基因的异常表达可能影响子宫内膜容受性,从而造成植入失败引起不孕。而近期,促排卵周期子宫内膜基因的表达成为学者们研究的热点,人们正努力寻找能用于指导临床的子宫内膜容受性相关基因,这对了解植入失败原因、评估子宫内膜功能和预测妊娠结局将起到重要作用。     

辅助生殖技术治疗中子宫内膜容受性标志变化的研究进展

子宫内膜容受性是妊娠建立的关键因素之一,在辅助生殖技术中,超生理水平的内分泌环境可能对子宫内膜容受性产生影响。子宫内膜厚度、内膜类型、子宫动脉及内膜下血流、子宫内膜胞饮突、外周血雌孕激素、白血病抑制因子(LIF)、基质金属蛋白酶(MMPs)、细胞黏附分子(CAMs)、Wnt信号转导系统、选择素、钙黏素、黏蛋白(MUC-1)、免疫球蛋白超家族(IG-SF)、血管内皮生长因子(VEGF)、肝素结合性表皮生长因子(HB-EGF)、集落刺激因子(CSF-1)、同源框基因(Hox基因)、骨桥蛋白、补体衰变加速因子、生长停滞和DNA损伤诱导蛋白、载脂蛋白D、Dickkopf/DKK1、单胺氧化酶A、白介素-15、促分裂活化蛋白激酶5、olfactomedin相关的雌激素受体位点蛋白。到目前为止,还没有一种分子标志物能成功地运用到临床作为子宫内膜容受性的标志。因此,寻找潜在的内膜容受性标志物的工作仍在继续进行。     

辅助生殖周期中超促排卵对子宫内膜容受性的影响

随着辅助生殖技术水平不断提高,子宫内膜容受性成为制约临床妊娠率提高的关键因素。促排卵应用的大量性激素类药物,以及因为多个卵泡发育引起的体内一系列远超正常生理的激素水平和蛋白因子的改变,都有可能会对子宫内膜容受性造成一定的影响。鉴于国内外现有的研究主要从子宫内膜超声形态学、组织学、分子生物学及基因组学对子宫内膜容受能力进行评估,文章也将从这几个方面论述超促排卵对子宫内膜容受性的影响。     

Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model

OBJECTIVE: To investigate the effect of levonorgestrel and mifepristone on the expression of endometrial receptivity markers in a three-dimensional endometrial construct. DESIGN: In vitro study. SETTING: University hospital and research laboratory. PATIENT(S): Twelve fertile donors. INTERVENTION(S): Timed endometrial biopsy. MAIN OUTCOME MEASURE(S): Examine the effect of levonorgestrel along with another well-studied fertility-regulating drug, mifepristone, on the expression of endometrial receptivity factors in a three-dimensional stromal and epithelial cell coculture model by immunohistochemistry. RESULT(S): Both epithelial and stromal cells of in vitro endometrial construct showed the presence of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptors-(A+B), vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1 beta, and cyclooxygenase-2, whereas the expression of progesterone receptor-B (AR), integrin alpha(V)beta(3,) and MUC1 were confined to epithelial cells. Mifepristone up-regulated expression of epithelial estrogen receptor-beta and progesterone receptor-B and down-regulated stromal vascular endothelial growth factor and surface molecules MUC1 and integrin alpha(V)beta(3) as observed in vivo. Levonorgestrel had no effect on the expression of endometrial receptivity markers studied. CONCLUSION(S): This in vitro model expresses progesterone-regulated endometrial receptivity factors seen in the physiologic condition. Treatment with levonorgestrel did not affect the expression of these endometrial receptivity markers in contrast to mifepristone. This in vitro model holds the potential to study endometrial receptivity, the embryo-endometrial interaction, and develop new agents for fertility control.     

子宫内膜容受性的无创性评价

子宫内膜容受性是胚胎着床、成功妊娠的必要条件。对子宫内膜容受性进行评估是辅助生育技术中重要的一环。其评价指标有很多,目前应用较为广泛的包括内膜活检、超声检查、内分泌检查和内膜分泌物分析等。内膜活检法因其创伤性使临床应用受到限制;超声虽能简便有效地预测内膜容受性,但存在很大的争议;激素及分子生物学指标从分子生物学方面阐明了影响内膜容受性的重要因素,具有其独特的临床应用价值;内膜分泌物分析在评价子宫内膜容受性方面,具有无创性、信息量大等优势,近年来正在成为生殖领域研究的热点。     

Current molecular aspects of the carcinogenesis of the uterine endometrium

Abstract. Inoue M. Current molecular aspects of the carcinogenesis of the uterine endometrium.
Carcinogenesis in many tissues is a multistep process accompanied by a variety of morphologic, biochemical, and genetic changes in each step. It is well known that endometrial cancers arise through a series of precursor lesions, simple, complex, and atypical hyperplasia, by unopposed and prolonged estrogen stimulation. It is also accepted that there is an estrogen-independent type in which the precursor lesions are not identified. Recent molecular-based evidence has revealed three possible pathways for endometrial carcinogenesis, namely hyperplasia, metaplasia, and de novo pathways. The pathways each have their own features in both histopathology and molecular biology. Such understanding of the molecular profile of endometrial carcinoma prompted us to revise the classic criteria in histopathology regarding endometrial carcinogenesis. The recent molecular-based studies have provided a concept of endometrial intraepithelial lesions: endometrial intraepithelial neoplasia (EIN) as the precursor lesions of endometrial carcinomas. The new terminology might improve cancer screening protocols and treatment modalities.     

子宫内膜容受性的表观遗传调控机制的研究进展

表观遗传在调控子宫内膜容受性和胚胎植入方面有重要作用。表观遗传学调控参与月经周期子宫内膜再生和增殖、血管形成、植入和蜕膜化。DNA甲基化与EMs发生有关,卵巢癌相关的肿瘤抑制基因的高甲基化导致基因表达沉默,很多与子宫内膜癌相关的肿瘤基因都有异常甲基化变化,进而发生肿瘤。组蛋白修饰参与许多妇科疾病的发生过程,其中部分妇科疾病正是因为改变子宫内膜容受状态进而导致不孕。组蛋白修饰和DNA甲基化之间也可以相互调控,同时组蛋白乙酰化也可以调节DNA甲基化。缺少miRNA的表达与某些人类子宫内膜疾病相关,例如EMs、子宫内膜增生和肿瘤,这些疾病影响子宫内膜的厚度、血流状态、分子表达进而降低子宫内膜的容受性,导致不孕。     

三维超声联合子宫内膜采集器在子宫内膜癌筛查中的应用#br#

Objective?To explore the value of three-dimensional ultrasound combined with disposable endometrial cell samplers in endometrial carcinoma screening. Methods?108 women with vaginal bleeding after menopause, abnormal uterine bleeding, vaginal discharge and other suspected symptoms from Jaunary 2018 to December 2020 in The Second Affiliated Hospital of Zhengzhou University were involved. The endometrium was collected by three-dimensional ultrasound combined with endometrial cell samplers, cytology and histology performed simultaneously. Benign endometrial lesions were defined as negative, endometrial dysplasia and endometrial carcinoma as positive. Results?Among the 102 patients (excluding the successful patients who had not been brushed), 56 patients (54.90%) were pathologically diagnosed as benign lesions, 46 patients (45.10%) were diagnosed as endometrial carcinoma or atypical hyperplasia. Compared with the pathological results, the diagnostic coincidence rates of three-dimensional ultrasound, endometrial collector and combined examination were 88.24%, 93.14% and 97.06%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the combined examination were 96.00%, 100.00%, 100.00% and 96.43%, respectively. Conclusion?Three-dimensional ultrasound combined with disposable endometrial cell samplers has high diagnostic accuracy and is easy to operate in the screening of endometrial carcinoma, which is expected to be an ideal screening method for endometrial carcinoma.     

子宫内膜损伤宫腔粘连评价指标的临床应用北大核心CSCD

各种原因引起的子宫内膜基底层损伤可导致子宫内膜纤维化及宫腔形态学破坏。临床上最常见的子宫内膜损伤代表性疾病是宫腔粘连。子宫内膜损伤宫腔粘连的主要临床表现为月经量减少、闭经、不孕;临床评价指标包括影像学、宫腔镜形态学及子宫内膜容受性指标。中华医学会妇产科学分会妇科内镜学组制定的宫腔粘连评分分级标准纳入了更全面有效的评价指标,对于子宫内膜损伤的精准评估、诊断及生殖预后结局的有效预测具有更高的临床应用价值。     

Live birth after embryo transfer in an unresponsive thin endometrium

A healthy term livebirth in a 35-year-old woman with ovarian failure, hypoplastic uterus and atrophic endometrium after cancer treatment with chemotherapy and radiotherapy was achieved by ovum donation. The detection of a receptive endometrium using a new diagnostic tool of endometrial receptivity encouraged the medical team to carry on with this poor prognosis case. To the best of our knowledge, here we report the thinnest endometrium to date in which a healthy, full term live birth has been described in assisted conception.     

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。