补肾活血方中药对妊娠大鼠子宫内膜容受性的影响

目的:观察补肾活血方中药对妊娠大鼠子宫内膜容受性的影响.方法:选用妊娠SD大鼠随机分为空白组、模型组和中药组,于妊娠第l天模型组和中药组大鼠皮下注射米非司酮溶液1次(米非司酮溶液5 g/L,5 mg/kg)造成胚泡着床障碍模型,空白组皮下注射生理盐水1次(1 mL/kg).空白组和模型组从妊娠第l天起予生理盐水灌胃(6.7 mL/kg),2次,d,连续5 d.中药组从妊娠第1天起行补肾活血方中药灌胃(7.6g生药/kg),2次,d,连续5d.于妊娠第5天扫描电镜观察各组子宫内膜胞饮突发育情况,逆转录聚合酶链反应(RT-PCR)检测子宫内膜整合素αvβ3mRNA的表达,于妊娠第10天计数各组大鼠胚泡着床数.结果:模型组子宫内膜表面未见明显的胞饮突发育,表现为增生早期的子宫内膜变化.中药组可见发育中的胞饮突,发育形态明显超前于模型组,接近于空白组;模型组αvβ3mRNA表达水平(0.854 5±0.0747,0.3984±0.093 7)显著低于空白组(1.051 8±0.087 8,0.601 6±0.133 8)(P<0.01),中药组αvβ3mRNA表达水平(0.987 6±0.075 1,0.539 6±0.058 4)显著高于模型组(P<0.05);模型组胚泡着床数(4.63±3.66)显著低于空白组(12.63±2.07)(P<0.01),中药组胚泡着床数(10.75±2.44)显著高于模型组(P<0.01).结论:补肾活血方中药能明显改善胚泡着床障碍大鼠子宫内膜表面胞饮突的发育,并显著提高子宫内膜整合素αvβ3mRNA的表达,有助于子宫内膜容受性的建立,从而最终提高胚泡的着床率.     

人脐带间充质干细胞治疗大鼠子宫内膜损伤的研究

目的:探讨人脐带间充质干细胞(hUC-MSCs)移植对子宫内膜损伤大鼠的治疗作用及可能作用机制。方法:用无水乙醇诱导大鼠子宫内膜损伤模型,分为模型组、对照组、干细胞治疗组、雌激素治疗组。HE染色法观察子宫内膜组织学变化,测定子宫内膜厚度,免疫组化法检测血管内皮生长因子(VEGF)、雌激素受体(ERα)以及整合素β3表达。结果:对照组的子宫内膜厚度高于其他组(P0.05),其余组间差异不明显。与对照组相比,模型组的VEGF、ERα、整合素β3表达均降低(P0.05);与模型组相比,干细胞治疗组、雌激素治疗组的VEGF、ERα、整合素β3表达均升高(P0.05);与雌激素治疗组相比,干细胞治疗组的VEGF、ERα、整合素β3表达均升高(P0.05)。结论:hUC-MSCs移植和雌激素治疗均可不同程度地修复大鼠子宫内膜损伤组织,改善子宫内膜容受性,干细胞移植疗效优于单纯雌激素治疗。     

控制性超排卵周期的子宫内膜容受性研究

目的 研究控制性超排卵(COH)对子宫内膜容受性的影响。方法 扫描电镜观察COH后子宫内膜胞饮突的变化和免疫组化法检测整合素β3、TGFβl的表达；以正常月经周期分泌中期子宫内膜作对照。结果 COH周期，完全发展的胞饮突出现在月经周期的第18—19d，较正常周期提前l一2d出现和消失；整合素β3、TGFβl在正常月经周期第2l一23d的子宫内膜腔上皮和腺上皮细胞的细胞质高表达，而COH周期在第18—20d高表达。COH周期和正常周期，整合素β3和TGFβl在子宫内膜上皮细胞的高表达与完全发展胞饮突的出现在时期上存在着一致性。结论 COH可能通过改变子宫内膜与着床密切相关的粘附分子、细胞因子和超微结构的时序性表达来影响子宫内膜的容受性，使子宫内膜着床窗的开放与胚泡的发育不同步，这可能是影响IVF妊娠率的重要原因。     

三维或二维培养间充质干细胞联合水凝胶治疗宫腔粘连大鼠的疗效比较

目的:比较三维培养人脐带间充质干细胞(3D-hUC-MSCs)或二维培养人脐带间充质干细胞(2D-hUC-MSCs)联合水凝胶应用于宫腔粘连(IUA)大鼠的疗效差异。方法:将32只雌性SD大鼠随机分为正常对照组、模型对照组、2D治疗组和3D治疗组各8只。将2D-hUC-MSCs贴附在微载体制备成3D-hUC-MSCs。采用机械刮宫+脂多糖感染双重损伤法构建IUA大鼠，对IUA大鼠进行2D-hUC-MSCs或3D-hUC-MSCs联合水凝胶治疗。用HE染色检测子宫内膜腺体数目，Masson染色检测子宫内膜纤维化面积比，免疫组化法检测子宫内膜整合素αVβ3表达，通过合笼实验评价妊娠结局。结果:与模型对照组相比，2D治疗组和3D治疗组大鼠的子宫内膜腺体数明显增加、纤维化显著减少，且3D治疗组效果接近于正常对照组水平。在大鼠子宫内膜αVβ3表达和胎鼠数目方面，2D治疗组与模型对照组比较差异无统计学意义，而3D治疗组较模型对照组明显改善，且接近于正常对照组水平。结论:3D-hUC-MSCs联合水凝胶可有效改善IUA大鼠子宫内膜纤维化、子宫内膜容受性及妊娠结局，并且相比于2D-hUC-MSCs联合...     

补肾活血方中药对妊娠大鼠子宫内膜容受性的影响

目的：观察补肾活血方中药对妊娠大鼠子宫内膜容受性的影响。方法：选用妊娠SD大鼠随机分为空白组、模型组和中药组,于妊娠第1天模型组和中药组大鼠皮下注射米非司酮溶液1次（米非司酮溶液5g／L,5mg／kg）造成胚泡着床障碍模型,空白组皮下注射生理盐水1次（1mL／kg）。空白组和模型组从妊娠第1天起予生理盐水灌胃（6．7mL／kg）,2次/d,连续5d。中药组从妊娠第1天起行补肾活血方中药灌胃（7．6g生药／kg）,2次/d,连续5d。于妊娠第5天扫描电镜观察各组子宫内膜胞饮突发育情况,逆转录聚合酶链反应（RT-PCR）检测子宫内膜整合素αvβ3mRNA的表达,于妊娠第10天计数各组大鼠胚泡着床数。结果：模型组子宫内膜表面未见明显的胞饮突发育,表现为增生早期的子宫内膜变化,中药组可见发育中的胞饮突,发育形态明显超前于模型组,接近于空白组;模型组αvβ3mRNA表达水平（0．8545±0．0747,0．3984±0．0937）显著低于空白组（1．0518±0．0878,0．6016±0．1338）（P〈0．01）,中药组俚届3mRNA表达水平（0．9876±0．0751,0．5396±0．0584）显著高于模型组（P〈0．05）;模型组胚泡着床数（4．63±3．66）显著低于空白组（12．63±2．07）（P〈0．01）,中药组胚泡着床数（10．75±2．44）显著高于模型组（P〈0．01）。结论：补肾活血方中药能明显改善胚泡着床障碍大鼠子宫内膜表面胞饮突的发育,并显著提高子宫内膜整合素αvβ3mRNA     

HCG、LH对子宫内膜白血病抑制因子和整合素β3表达的影响

目的:观察小鼠子宫内膜容受性相关因子的改变,包括白血病抑制因子(LIF)和整合素β3表达的变化,来探讨人绒毛膜促性腺激素(HCG)或黄体生成素(LH)的使用对小鼠子宫内膜容受性的影响。方法:选取30只昆明小鼠,药物降调后进行人工周期,然后根据注射药物的不同分为HCG组、LH组和对照组3组,处死小鼠并取出小鼠子宫内膜。免疫组化SP法检测LIF和整合素β3在子宫内膜上的表达,并应用计算机图像分析系统检测其表达阳性率的变化。结果:HCG组子宫内膜LIF和整合素β3的表达均低于对照组,差异有统计学意义(P<0.05)。LH组子宫内膜LIF和整合素β3表达与对照组相比较,差异无统计学意义。结论:HCG的使用可以影响子宫内膜的LIF以及整合素β3的表达,而在一定程度上使子宫内膜的容受性下降,而LH的使用对子宫内膜的容受性的影响不明显。     

大鼠子宫内膜损伤模型的建立与评价

目的 建立大鼠子宫内膜损伤模型,并对模型进行评价。方法 选取SD大鼠26只,每只大鼠左侧子宫作为模型组,右侧子宫作为对照组,左侧子宫宫腔注入体积分数95%乙醇0.3~0.5 m L持续5 min建立模型,右侧子宫注入等量生理盐水,术后2个动情周期后切除子宫,观察子宫内膜形态学改变,子宫内膜厚度及内膜损伤程度评分,用免疫组织化学方法检测子宫内膜表面中角蛋白(cytokeratin,CK18)、波形蛋白(vimentin)、整合素β3(integrinβ3)的表达。结果 与对照组相比,模型组子宫质硬、粗细不均,形态不规则,宫壁厚薄不均,HE染色子宫内膜上皮细胞排列紊乱,间质充血、水肿,腺体数量减少,测得子宫内膜厚度明显变薄,损伤程度明显升高,免疫组织化学测得模型组CK18、波形蛋白、整合素β3的表达明显低于对照组,差异有统计学意义(P0.05)。结论 体积分数95%乙醇可成功、有效地建立大鼠子宫内膜损伤的动物模型。     

GnRHa对改善他莫西芬诱发子宫腺肌病小鼠模型内膜容受性的作用

目的:探讨促性腺激素释放激素激动剂(GnRHa)对腺肌病模型小鼠种植窗期内膜容受性的影响。方法:新生ICR小鼠滴喂他莫西芬建立子宫腺肌病模型,随机分为GnRHa降调的模型鼠组(A组)、模型对照鼠组(B组),并取同龄正常小鼠作为对照组(C组),每组8只,于100~115日龄处死,HE染色检测小鼠子宫病理变化;免疫组织化学CD31染色计算小鼠子宫微血管密度;免疫组织化学法检测种植窗期子宫内膜LIF表达及扫描电镜下观察胞饮突发育情况。结果:①口服他莫西芬法建立ICR小鼠子宫腺肌病模型造模率为100%,B组小鼠子宫肌层微血管密度高于A、C组,差异有统计学意义(P<0.05)。②种植窗期子宫内膜LIF蛋白水平A组和C组明显高于B组,差异有统计学意义(P<0.05);A、C组间无统计学差异(P>0.05)。③B组可见较多退化的胞饮突,分布稀疏,呈局灶性分布;A组的胞饮突较B组丰富但大小略不均;C组胞饮突分布较丰富且发育完全。结论:新生小鼠口服他莫西芬法可高效建立子宫腺肌病模型,GnRHa降调节能改善子宫腺肌病小鼠子宫内膜中LIF表达及胞饮突发育,从而提高子宫内膜容受性。     

GnRHa长方案超促排卵对围着床期小鼠子宫内膜溶血磷脂酸受体3(LPAR3)蛋白的表达及胞饮突发育的影响

目的:研究GnRHa/hMG/hCG控制性超促排卵对围着床期小鼠子宫内膜溶血磷脂酸受体3(LPAR3)蛋白的表达及胞饮突发育的影响。方法:雌性未孕昆明系小鼠72只,随机分为控制性超促排卵组(COH)和自然受孕组(NC),再按交配成功后天数每组分成4个亚组,接受相应的建模处理。用Western blotting检测性交后3~6 d(孕3~6 d)小鼠子宫内膜LPAR3蛋白的表达;同时用扫描电子显微镜观察子宫内膜胞饮突的发育。结果:COH组性交后3 d亚组LPAR3蛋白表达最强,NC组4 d亚组表达最强,但两者表达量无显著差异。COH组3~5 d亚组胞饮突发育不同步,大小不一,胞饮突数量较NC组相应时间明显减少,呈局灶性分布。NC组3 d亚组多为发育中的胞饮突,4 d亚组几乎均为完全发育的胞饮突,5 d亚组多为退化的胞饮突。结论:GnRHa控制性超促排卵可能通过改变小鼠子宫内膜LPAR3蛋白和超微结构的时序变化来影响子宫内膜容受性,从而影响胚泡着床。     

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。     

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.     

Endometrial pinopodes: some more understanding on human implantation?

Endometrial receptivity is a prerequisite for blastocyst implantation. During receptivity, the hairy-like epithelial cell microvilli transiently fuse to a single flower-like membrane projection called the 'pinopode'. Scanning electron microscopy in sequential endometrial biopsies shows that pinopodes appear about 1 week after ovulation, and they develop and regress within just 2 days. Interestingly, the cycle days when pinopodes appear can vary by up to 5 days between different individuals. On average, they occur on days 20-21 in natural cycles and earlier (days 19-20) in stimulated cycles. The abundance of pinopodes relates to implantation success and many patients with multiple implantation failures fail to produce pinopodes. Based on these findings, biopsies from candidate embryo recipients have been examined in mock cycles and pinopode numbers and timing of their appearance assessed. A similar cycle follows where embryos are replaced earlier or later, according to the reported timing of pinopode formation. If pinopodes are absent, the cycle can be modified. Accumulating evidence supports their clinical use as a marker to assess endometrial receptivity. Pinopode appearance, loss of steroid receptors and maximal expression of a(v)b(3) integrin, osteopontin and leukaemia inhibitory factor and receptor have been demonstrated in the same biopsy, showing a consistent association of pinopode appearance and other receptivity changes.     

Altered expression of hormone receptor,integrin β3 and pinopode in the endometrium of luteal phase defect women

Objective: To invistigate estrogen receptor (ER), progesterone receptor (PR), integrin β3, and pinopode expression in luteal phase deficiency (LPD) women.

Methods: There were 52 nulligravidas consecutive infertile patients undergoing a routine assistant reproduction consultation included in this study. An endometrial biopsy sample was randomly obtained between days 4 and 10 of the luteal phase. Endometrial morphology was examined with scanning electron microscopy. Expressions of ER, PR, integrin β3 were determined in the endometrium of LPD patients with immunohistochemistry.

Results: The incidence of LPD was 15.3% (8/52) in this study. On day luteinizing hormone (LH) surge?+?9～LH?+?10, noted regressing pinopodes resembling a day LH?+?7～LH?+?8 in the endometrium of the control group. The expressions of ER and PR in glandular epithelium were significantly increased in endometrium of LPD than that in the control group (p?p?Conclusion: The altered expression of ER and PR may be associated with the expression variation of integrin and pinopode formation in endometrium of LPD women. This alteration may imply the association of low rates of cycle fecundity and high rates of embryonic loss in LPD women.     

来曲唑和克罗米酚对小鼠着床期子宫内膜容受性的影响

目的:探讨来曲唑和克罗米酚对小鼠着床期胞饮泡和白血病抑制因子(LIF)表达的影响。方法:将30只小鼠随机分为3组:来曲唑(LE)组(n=10)、克罗米酚(CC)组(n=10)及对照组(n=10)。促排卵后妊娠d4．5取小鼠子宫,采用扫描电镜观察3组子宫内膜胞饮突的变化以及免疫组化技术检测子宫内膜LIF的表达强弱。结果:在3组妊娠天数一致的情况下,LE组中无论是子宫内膜胞饮突,还是LIF的表达,均与对照组相似。而CC组的表达显著弱于前二组。结论:与CC促排卵相比,LE不影响小鼠着床期子宫内膜超微结构和相关基因LIF的表达,然而CC组子宫的容受性呈现一定的抑制性。     

Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors

OBJECTIVE: To investigate the relation between the development of endometrial pinopodes and the serum concentration of hormones and the distribution of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and progesterone receptor B. DESIGN: Prospective clinical study. SETTING: Hospital-based unit of reproductive health and university-affiliated reproductive research laboratories. PATIENT(S): Twenty-seven healthy fertile women with normal menstrual cycles. INTERVENTION(S): Urine and blood sampling for hormone measurement, vaginal ultrasonography, and endometrial biopsy. MAIN OUTCOME MEASURE(S): Appearance of the endometrium on light microscopy, pinopode formation, serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and expression of progesterone receptors A and B and estrogen receptors alpha and beta. RESULT(S): Pinopode formation and regression were closely associated with increases and decreases, respectively, in serum progesterone concentration. At pinopode development, levels progesterone receptors A and B in the glandular and luminal epithelial cells decreased; this effect was mainly dependent on the absence of progesterone receptor B. Serum estrogen levels and levels of estrogen receptor alpha and beta did not correlate with pinopode formation. CONCLUSION(S): The increase in serum progesterone level and down-regulation of progesterone receptor B are important in development of pinopodes.     

Synchronous expression of pinopodes and alpha v beta 3 and alpha 4 beta 1 integrins in the endometrial surface epithelium of normally menstruating women during the implantation window

OBJECTIVE: To use histology, scanning electron microscopy (SEM) and immunohistochemistry to examine the expression of pinopodes, and alpha v beta 3 and alpha 4 beta 1 integrins in the same endometrial biopsies. STUDY DESIGN: A prospective observational study. Fifteen consecutive regularly menstruating women with normal hormone profiles were followed for detection of ovulation and then biopsied twice, on postovulatory days luteinizing hormone (LH) +6 and LH +8. Measurements included abundance and development stage of pinopodes and a semiquantitative assessment of intensity of antibody staining for integrins. RESULTS: All biopsies observed under light microscopy showed an in-phase endometrium. Pinopodes were found developing mostly on day LH +6 and were fully developed on day LH +8. The expression of alpha v beta 3 dimer increased significantly from day LH +6 to day LH +8, while alpha 4 beta 1 dimer did not show any significant change during the same period. Fully developed pinopodes and strong intensity of alpha v beta 3 integrin were the most common findings. CONCLUSION: These results indicate a coordinated, synchronous change in morphology and adhesion molecule expression of endometrial epithelial cells on day LH +8 of a normal menstrual cycle.     

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.     

Endometrial receptivity: changes in cell-surface morphology

Ovulation and fertilization trigger embryonic development and endometrial differentiation by corpus luteum progesterone production. These two synchronous processes couple about 1 week later, when the blastocyst begins to implant in the now receptive endometrium (implantation window). Receptivity is a state of endometrial differentiation marked by a change in epithelial morphology: the hairy-like cell microvilli fuse to a single flower-like membrane projection called the "pinopode." Scanning electron microscopy of sequential endometrial biopsies shows that pinopodes form briefly (1-2 days), and their numbers correlate with implantation. On average, the formation of pinopodes is earlier in stimulated (days 19-20) and later in artificial (days 21-22) compared with natural cycles (days 20-21). There is, however, a wide (up to 5 days) variation between women in the cycle days on which pinopodes form. These results suggest the existence of a narrow and discrete implantation window in humans. Detection of pinopodes is a potential clinical marker to assess endometrial receptivity.     

输卵管积水妇女种植窗期子宫内膜胞饮小泡及部分种植因子的变化

目的:探讨输卵管积水对种植窗期子宫内膜胞饮小泡及种植因子integrinβ3、MUC1及LIF表达的影响。方法:选择接受IVF治疗的20例输卵管积水妇女(积水组)及21例因男性因素所致不孕的妇女(对照组),在种植窗期间通过扫描电镜观察子宫内膜表面胞饮小泡的形态、密度,免疫组织化学分析种植因子integrinβ3、MUC1及LIF的表达。结果:对照组成熟期胞饮小泡所占比例以及胞饮小泡的密度与积水组相比无统计学差异(P>0.05)。integrinβ3、LIF及MUC1在正常对照组的腺上皮细胞和腔上皮细胞中的表达强度均明显高于积水组,integrinβ3在间质细胞中表达亦明显高于积水组。结论:integrinβ3、MUC1及LIF受积水的影响较胞饮小泡更为敏感,先于子宫内膜表面超微结构受到改变,可能是造成胚胎种植率下降的主要原因之一。     

Effect of irisin on endometrial receptivity of rats with polycystic ovary syndrome

Abstract

To investigate the influence of irisin on endometrial receptivity of rats with polycystic ovarian syndrome (PCOS). PCOS rats were randomly divided into PCOS group and irisin group, and normal rats were used as control group. The PCOS group and control group were injected intraperitoneally with normal saline while the irisin group with recombinant irisin. The serum and uterus were obtained. Detect serum sex hormones, including Testosterone (T), Estradiol (E₂), Progesterone (P), and glucose, insulin levels. Observe endometrial morphology by hematoxylin-eosin staining. Then evaluate the expression of leukemia inhibitory factor (LIF) and integrin αvβ3 in endometrium using ELISA, immunohistochemistry and Real-time PCR. (1) Levels of serum T, glucose and insulin in PCOS group were significantly higher than those in control and irisin group. (2) For the endometrial morphology, levels of equivalent diameter, area of uterine glands and gland cavity and endometrial average thickness were lower in PCOS group than those in control and irisin group. (3) LIF and integrin αvβ3 mRNA were basically consistent with protein expression. Levels of LIF and integrin αvβ3 were decreased in PCOS group when compared with control and irisin group. Irisin may improve endometrial receptivity by promoting expression of LIF and integrin αvβ3.