月经周期中白血病抑制因子的变化与子宫内膜容受性的关系
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摘要
目的通过测定育龄期不孕妇女卵泡早期、采卵日、黄体中期血清和卵泡液及子宫内膜中白血病抑制因子(LIF)的含量,探讨LIF与种植窗期子宫内膜容受性的关系,从多层面上阐明LIF在月经周期中的变化规律及其与子宫内膜容受性的相互关系,揭示LIF在胚胎种植过程中的可能作用机制,进而为提高人类辅助生殖技术的胚胎种植率和临床妊娠率提供理论依据。
方法选择在宁夏医科大学附属医院生殖医学中心首次实施体外受精-胚胎移植(IVF-ET)/卵泡浆内单精子显微注射(ICSI)治疗的不孕症妇女48例,应用实时荧光定量聚合酶联反应(RT-PCR)方法测定同一月经周期卵泡早期、黄体中期子宫内膜LIFmRNA的表达,并采集同日血清以及IVF-ET周期中采卵日的血清及卵泡液,应用ELISA法测定血清及卵泡液LIF的含量;采用SPSS11.5统计软件分析。计量资料用t检验,计数资料用x2检验,各指标间的相关关系用Pearson分析。
结果(1)卵泡早期、采卵日、黄体中期血清LIF含量有显著性差异(P<0.05),两两比较采卵日血清LIF含量明显高于卵泡早期和黄体中期,黄体中期略高于卵泡早期;(2)卵泡早期子宫内膜LIFmRNA表达量明显高于黄体中期(20.70±12.15vs1.07±1.48,P<0.05);(3)卵泡早期、采卵日、黄体中期血清E2、P有显著性差异(P<0.001),两两比较采卵日明显高于卵泡早期和黄体中期,黄体中期高于卵泡早期;(4)黄体中期子宫内膜LIFmRNA表达量与血清中P含量呈显著正相关(r=0.287,P<0.05);(5)采卵日血清与左右侧卵泡液中LIF含量呈明显正相关(右侧r=0.808,左侧r=0.405,P均<0.05);(6)采卵日血清及左右侧卵泡液中LIF含量与E2含量均呈显著正相关(血清r=0.990,右侧r=0.893,左侧r=0.968,P均<0.05);(7)采卵日血清LIF含量与实验室获卵数呈显著正相关(r=0.659,P<0.05);左右侧卵泡液LIF含量亦与同侧获卵数呈明显正相关(右侧r=0.540,左侧r=0.431,P均<0.05);采卵日右侧卵泡液中LIF含量高于左侧(67.28±46.15vs54.44±33.09, P=0.052);(8)妊娠组卵泡早期血清LIF含量明显低于非妊娠组(P<0.05),而采卵日、黄体中期两组无明显差异;(9)妊娠组采卵日血清和左右侧卵泡液中LIF含量与血清中E2水平呈显著正相关(血清r=0.505,右侧r=0.497,左侧r=0.572,P均<0.05);(10)女性因素组的卵泡早期和黄体中期子宫内膜LIFmRNA表达量均明显低于男方因素组(卵泡早期17.93±9.36vs30.04±15.95,黄体中期0.66±0.77vs2.42±2.35,P均<0.05);(11)采卵日女性因素组血清和卵泡液LIF含量与血清E2呈显著正相关(血清r=0.504,右侧r=0.471,左侧r=0.420,P均<0.05)。
结论(1)卵泡早期、采卵日、黄体中期血清LIF含量有显著性差异,提示月经周期中LIF来源的部位随时相而异;卵泡早期子宫内膜LIFmRNA的表达明显高于黄体中期,表明子宫内膜是其主要来源;而采卵日血清LIF含量与左右侧卵泡液中LIF含量呈明显正相关,显示IVF-ET周期中采卵日血清LIF主要来源于卵巢;(2)卵泡早期、采卵日、黄体中期血清LIF水平的变化趋势与血清中E2、P含量曲线一致,说明E2、P直接参与调节生殖周期中LIF的产生;(3)黄体中期子宫内膜LIFmRNA的表达与血清中P含量呈显著正相关,表明血清P可能通过内膜P受体上调子宫内膜中LIFmRNA的表达,影响子宫内膜接受胚胎的能力;(4)采卵日血清中LIF含量与获卵数呈显著正相关,血清及左右侧卵泡液中LIF含量与血清中E2水平也呈显著正相关,且左右侧卵泡液中LIF含量与左右侧获卵数呈明显正相关,右侧卵泡液中LIF高于左侧,说明采卵日血清和卵泡液中LIF含量与获卵数量密切相关,右侧卵巢成熟卵泡及获卵数多于左侧卵巢;(5)女性因素组卵泡早期及黄体中期子宫内膜LIFmRNA的表达均明显低于男方因素组,提示无论何种原因引起的女性不孕,子宫内膜中LIFmRNA的表达水平均减退,使子宫内膜容受性降低,进而为不明原因的原发和继发不孕患者提供了分子病因学依据;(6)女性因素组采卵日血清和左右侧卵泡液中LIF含量与血清中E2呈明显正相关,提示子宫内膜异位症和盆腔输卵管因素均可影响卵子的生长和成熟环境;(7)深入研究LIF在胚胎着床中的作用机理及调节因素,有可能为提高临床妊娠率和研制新型的抗着床药物提供理论依据。
Objective To investigate the variation rule of leukemia inhabitory factor(LIF) by analysizing the content of LIF in serum,follicle fluid(FF) and endometrium of infertile women in follicle phase,ovum pick-up(OPU) day and midluteal phase, and illuminate the correlation between LIF and the endometrium reception ability, and mechanism of LIF in the process of embryo implantation for improving the embryo implantation rate and the clinic pregnancy rate in assisted reproductive technology.
Methods 48 IVF/ICSI firstly cycles were researched in the center for reproductive medicine of the affiliated hospital of Ningxia Medical University.LIF content of the endometrium in the earlier follicle phase and midluteal phase was measured by RT-PCR,and serum LIF examined by ELISA. Paired t-test ,Chi-Square Test and Pearson correlate were used in analysis of data.
Results (1) Serum LIF content on OPU day was significantly higher than that in the earlier follicle phase and midluteal phase(P<0.05); (2) LIFmRNA expression of endometrium was obviously higher in the earlier follicle phase than that in the midluteal phase (20.70±12.15vs1.07±1.48,P<0.05); (3) Serum E2 and P on OPU day were significantly higher than in the earlier follicle phase and midluteal phase(P<0.001),while there was lightly higher in the midluteal phase than in the earlier follicle phase; (4) LIFmRNA of the endometrium in the midluteal phase was positively correlated with the serum P (r=0.287,P<0.05); (5) Serum LIF content on OPU day was positively correlated with that in bilateral FF(right ovary,r=0.808,left ovary,r=0.405,P all<0.05); (6) The serum LIF density and bilateral FF on the OPU day was positively correlated with the serum E2 content(serum,r=0.990,right ovary,r=0.893,left ovary,r=0.968,Pall <0.05); (7) Serum and bilateral FF LIF content on the OPU day were positively correlated with the retrieved follicle numbers (serum,r=0.659,right ovary, r=0.540, left ovary,r=0.431,P all<0.05). LIF content in the right FF was higher than that in the left(67.28±46.15vs54.44±33.09, P=0.052); (8) Serum LIF content of the earlier follicle phase in the pregnancy group was obviously lower than the non-pregnancy group(P<0.05); (9) LIF content in the serum and bilateral FF on OPU day in the pregnancy group were positively correlated with serum E2(serum,r=0.505,right ovary,r=0.497,left ovary,r=0.572,P<0.05); (10) Of the earlier follicle phase and midluteal phase, the endometrium LIF mRNA in female factor infertility group was obviously lower than those in the male infertility group(the earlier follicle phase,17.93±9.36vs 30.04±15.95,the midluteal phase,0.66±0.77vs2.42±2.35,P<0.05); (11) LIF density in serum and FF in the female infertility group was positively correlated whth serum E2(serum,r=0.504,right ovary,r=0.471, left ovary,r=0.420,P<0.05).
Conclusions (1) LIF resource locations are different with the phases in menstrual cycle.The main resource of serum LIF is mononuclear cell and macrophage in the earlier follicle phase and midluteal phase.Ovary is the main resource of the serum LIF on the OPU day in IVF-ET cycles; (2) Serum LIF level is consistent with serum E2 and P, indicating that E2 and P participate directly to accommodate LIF creation in reproductive cycle; (3) Serum P can upregulate LIF mRNA expression in endometrium to affect the endometrium receptivity via the P receptor; (4) LIF level in the serum and FF is intimately correlated with the retrieval follicle numbers,and the mature follicle numbers in the right ovary are more than the left; (5) Whatever reasons that induce the female infertility downgrade LIF mRNA expression in the endometrium, and decrease the endometrium reception ability,which can provide molecular etiology for unexplained primary and secondary infertility; (6) Endometriosis, pelvic cavity adhision and fallopian tube disease can have influence on the mature environment of ovum growth.(7) Further investigate the mechanism of regulation factors of LIF to provide theory basis for developing a new anti-implantation therapy.
方法选择在宁夏医科大学附属医院生殖医学中心首次实施体外受精-胚胎移植(IVF-ET)/卵泡浆内单精子显微注射(ICSI)治疗的不孕症妇女48例,应用实时荧光定量聚合酶联反应(RT-PCR)方法测定同一月经周期卵泡早期、黄体中期子宫内膜LIFmRNA的表达,并采集同日血清以及IVF-ET周期中采卵日的血清及卵泡液,应用ELISA法测定血清及卵泡液LIF的含量;采用SPSS11.5统计软件分析。计量资料用t检验,计数资料用x2检验,各指标间的相关关系用Pearson分析。
结果(1)卵泡早期、采卵日、黄体中期血清LIF含量有显著性差异(P<0.05),两两比较采卵日血清LIF含量明显高于卵泡早期和黄体中期,黄体中期略高于卵泡早期;(2)卵泡早期子宫内膜LIFmRNA表达量明显高于黄体中期(20.70±12.15vs1.07±1.48,P<0.05);(3)卵泡早期、采卵日、黄体中期血清E2、P有显著性差异(P<0.001),两两比较采卵日明显高于卵泡早期和黄体中期,黄体中期高于卵泡早期;(4)黄体中期子宫内膜LIFmRNA表达量与血清中P含量呈显著正相关(r=0.287,P<0.05);(5)采卵日血清与左右侧卵泡液中LIF含量呈明显正相关(右侧r=0.808,左侧r=0.405,P均<0.05);(6)采卵日血清及左右侧卵泡液中LIF含量与E2含量均呈显著正相关(血清r=0.990,右侧r=0.893,左侧r=0.968,P均<0.05);(7)采卵日血清LIF含量与实验室获卵数呈显著正相关(r=0.659,P<0.05);左右侧卵泡液LIF含量亦与同侧获卵数呈明显正相关(右侧r=0.540,左侧r=0.431,P均<0.05);采卵日右侧卵泡液中LIF含量高于左侧(67.28±46.15vs54.44±33.09, P=0.052);(8)妊娠组卵泡早期血清LIF含量明显低于非妊娠组(P<0.05),而采卵日、黄体中期两组无明显差异;(9)妊娠组采卵日血清和左右侧卵泡液中LIF含量与血清中E2水平呈显著正相关(血清r=0.505,右侧r=0.497,左侧r=0.572,P均<0.05);(10)女性因素组的卵泡早期和黄体中期子宫内膜LIFmRNA表达量均明显低于男方因素组(卵泡早期17.93±9.36vs30.04±15.95,黄体中期0.66±0.77vs2.42±2.35,P均<0.05);(11)采卵日女性因素组血清和卵泡液LIF含量与血清E2呈显著正相关(血清r=0.504,右侧r=0.471,左侧r=0.420,P均<0.05)。
结论(1)卵泡早期、采卵日、黄体中期血清LIF含量有显著性差异,提示月经周期中LIF来源的部位随时相而异;卵泡早期子宫内膜LIFmRNA的表达明显高于黄体中期,表明子宫内膜是其主要来源;而采卵日血清LIF含量与左右侧卵泡液中LIF含量呈明显正相关,显示IVF-ET周期中采卵日血清LIF主要来源于卵巢;(2)卵泡早期、采卵日、黄体中期血清LIF水平的变化趋势与血清中E2、P含量曲线一致,说明E2、P直接参与调节生殖周期中LIF的产生;(3)黄体中期子宫内膜LIFmRNA的表达与血清中P含量呈显著正相关,表明血清P可能通过内膜P受体上调子宫内膜中LIFmRNA的表达,影响子宫内膜接受胚胎的能力;(4)采卵日血清中LIF含量与获卵数呈显著正相关,血清及左右侧卵泡液中LIF含量与血清中E2水平也呈显著正相关,且左右侧卵泡液中LIF含量与左右侧获卵数呈明显正相关,右侧卵泡液中LIF高于左侧,说明采卵日血清和卵泡液中LIF含量与获卵数量密切相关,右侧卵巢成熟卵泡及获卵数多于左侧卵巢;(5)女性因素组卵泡早期及黄体中期子宫内膜LIFmRNA的表达均明显低于男方因素组,提示无论何种原因引起的女性不孕,子宫内膜中LIFmRNA的表达水平均减退,使子宫内膜容受性降低,进而为不明原因的原发和继发不孕患者提供了分子病因学依据;(6)女性因素组采卵日血清和左右侧卵泡液中LIF含量与血清中E2呈明显正相关,提示子宫内膜异位症和盆腔输卵管因素均可影响卵子的生长和成熟环境;(7)深入研究LIF在胚胎着床中的作用机理及调节因素,有可能为提高临床妊娠率和研制新型的抗着床药物提供理论依据。
Objective To investigate the variation rule of leukemia inhabitory factor(LIF) by analysizing the content of LIF in serum,follicle fluid(FF) and endometrium of infertile women in follicle phase,ovum pick-up(OPU) day and midluteal phase, and illuminate the correlation between LIF and the endometrium reception ability, and mechanism of LIF in the process of embryo implantation for improving the embryo implantation rate and the clinic pregnancy rate in assisted reproductive technology.
Methods 48 IVF/ICSI firstly cycles were researched in the center for reproductive medicine of the affiliated hospital of Ningxia Medical University.LIF content of the endometrium in the earlier follicle phase and midluteal phase was measured by RT-PCR,and serum LIF examined by ELISA. Paired t-test ,Chi-Square Test and Pearson correlate were used in analysis of data.
Results (1) Serum LIF content on OPU day was significantly higher than that in the earlier follicle phase and midluteal phase(P<0.05); (2) LIFmRNA expression of endometrium was obviously higher in the earlier follicle phase than that in the midluteal phase (20.70±12.15vs1.07±1.48,P<0.05); (3) Serum E2 and P on OPU day were significantly higher than in the earlier follicle phase and midluteal phase(P<0.001),while there was lightly higher in the midluteal phase than in the earlier follicle phase; (4) LIFmRNA of the endometrium in the midluteal phase was positively correlated with the serum P (r=0.287,P<0.05); (5) Serum LIF content on OPU day was positively correlated with that in bilateral FF(right ovary,r=0.808,left ovary,r=0.405,P all<0.05); (6) The serum LIF density and bilateral FF on the OPU day was positively correlated with the serum E2 content(serum,r=0.990,right ovary,r=0.893,left ovary,r=0.968,Pall <0.05); (7) Serum and bilateral FF LIF content on the OPU day were positively correlated with the retrieved follicle numbers (serum,r=0.659,right ovary, r=0.540, left ovary,r=0.431,P all<0.05). LIF content in the right FF was higher than that in the left(67.28±46.15vs54.44±33.09, P=0.052); (8) Serum LIF content of the earlier follicle phase in the pregnancy group was obviously lower than the non-pregnancy group(P<0.05); (9) LIF content in the serum and bilateral FF on OPU day in the pregnancy group were positively correlated with serum E2(serum,r=0.505,right ovary,r=0.497,left ovary,r=0.572,P<0.05); (10) Of the earlier follicle phase and midluteal phase, the endometrium LIF mRNA in female factor infertility group was obviously lower than those in the male infertility group(the earlier follicle phase,17.93±9.36vs 30.04±15.95,the midluteal phase,0.66±0.77vs2.42±2.35,P<0.05); (11) LIF density in serum and FF in the female infertility group was positively correlated whth serum E2(serum,r=0.504,right ovary,r=0.471, left ovary,r=0.420,P<0.05).
Conclusions (1) LIF resource locations are different with the phases in menstrual cycle.The main resource of serum LIF is mononuclear cell and macrophage in the earlier follicle phase and midluteal phase.Ovary is the main resource of the serum LIF on the OPU day in IVF-ET cycles; (2) Serum LIF level is consistent with serum E2 and P, indicating that E2 and P participate directly to accommodate LIF creation in reproductive cycle; (3) Serum P can upregulate LIF mRNA expression in endometrium to affect the endometrium receptivity via the P receptor; (4) LIF level in the serum and FF is intimately correlated with the retrieval follicle numbers,and the mature follicle numbers in the right ovary are more than the left; (5) Whatever reasons that induce the female infertility downgrade LIF mRNA expression in the endometrium, and decrease the endometrium reception ability,which can provide molecular etiology for unexplained primary and secondary infertility; (6) Endometriosis, pelvic cavity adhision and fallopian tube disease can have influence on the mature environment of ovum growth.(7) Further investigate the mechanism of regulation factors of LIF to provide theory basis for developing a new anti-implantation therapy.
引文
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[19]赵海波,何亚绒,李爱莉,等.人卵泡液中白血病抑制因子浓度及其对卵母细胞发育的影响.第四军医大学学报,2004,25(6):554-556.
[20] Piccinni MP,Scaletti C,Maggi E,et al,Role of hormonecontrolled Th1-and Th2-type cytokines in successful pregnancy.J Neuro immunol,2000,109(1):30-33.
[21] Arici A,Engin O,Attar E,et al.Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium. J Clin Endocrinol Metab,1995,80(6):1908-1914.
[22] Hambartsoumian E,Taupin J L,Moreau J F,et al.In vivo administration of progesterone inhibits the secretion of endometrial leukemia inhibitory factor in vitro.Mol Hum Reprod,1998,4(11):1039-1044.
[23] K. Wanggren, P.G. Lalitkumar, F. Hambiliki,et al. Leukaemia inhibitory factor receptor and gp130 in the human Fallopian tube and endometrium before and after mifepristone treatment and in the human preimplantation embryo. Mol Hum Reprod,2007,13(6):391-397.
[24] Sengupta J,Dhawan L,Ghosh D. Immunohistochemical localization of leukemia inhibitory factor, interleukins 1 and 6 at the primary implantation site in the rhesus monkey.Cytokine,2003,24(6):277-285.
[25] Fouladi Nashta AA, Andreu CV, Nijjar N, et al. Role of leukemia inhibitor factor(LIF) in decidualisation of murine uterine stromal cells in vitro. J Endocrinol,2004,181(3):477-492.
[26] Sawai K, Matsuzaki N, Okada T, et al. Human decidual cell biosynthesis of leukaemia inhibitory factor: regulation by decidualcytokinesand steroid hormones.BiolReprod,1997,56(5):1274-1280.
[27]李永丽,徐仙,赵君利,等.体外受精-胚胎移植术移植日子宫内膜容受性的超声学研究.中国妇幼保健,2009,35(5):16-18.
[28]李路,徐步芳,陈秋菊,等.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.生殖与避孕,2008,28(2):89-94.
[29]李蓉,乔杰,王威,等.多囊卵巢综合征患者着床窗口期子宫内膜容受性的改变.中国优生与遗传杂志,2007,15(10):23-25.
[30]王琳,史常旭,常青,等.白血病抑制因子在子宫内膜异位症并发不孕患者黄体中期子宫内膜中的表达.生殖与避孕,2002,22(6):355-357.
[31] Yu Xiao, Xiao Sun, Xiuli Yang, et al. Leukemia inhibitory factor is dysregulated in the endometrium and uterine flushing fluid of patients with adenomyosis during implantation window.Ferti and Steri,2009,3(1):1-5.
[32] Mikolajczyk M,Skrzypczak J,Szymanowski K,et al.The assessment of LIF in uterine flushing-a possible new diagnostic tool in states of impaired fertility. Reprod Biol,2003,3(3):259-270.
[33] Tsai HD,Chang CC,H sieh YY,et al.Leukemia inhibitory factor expression in different endometrial locations between fertile and infertile women throughout different menstrual phases [J].Assist Reprod Genet,2000,17(8): 415-418.
[34]董方莉,谭丽,郑英.植入窗期血清孕激素水平及子宫内膜白血病抑制因子表达对体外受精-胚胎移植结局的预测价值.生殖医学杂志,2007,16(1):20- 23.
[35] Emily B. Cullinan, Susan J. Abbondanzo, Patrick S. Anderson, et al. Leukemia inhibitory factor(LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. Acad Sci,1996,93(4):3115-3120.
[36] Jemma Evans,Rob D. Catalano,Pamela Brown,et al.Prokineticin 1 mediates fetal-maternal dialogue regulating endometrial leukemia inhibitory factor.THE FASEB J,2009,23(7):2165-2175.
[1]Aghajanova L. Leukemia inhibitory factor and human embryo implanta- tion[J]. Ann NY Acad Sci,2004,103(4):176-183.
[2] Guney M , Erdemoqlu E , Oral B , et al. Leukemia inhibitory factor (LIF) is immunohistochemically localized in tubal ectopic pregnancy[J].Acta Hostpcjem,2008,110(4): 319-323.
[3] DING Tian-bing,SONG Haengseok,WANG Xiao-hong,et al. Leukemia inhibitory factor ligand-receptor signaling is important for uterine receptivity and implantation in golden hamsters (Mesocricetus auratus)[J]. Reproduction,2008,135(1):41-53.
[4] Kralickova M,Sima R,Vanecek T,et al. Leukemia inhibitory factor gene mutations in the population of infertile women are not restricted to nulligravid patients [J]. Eur J Obstet Gynecol Reprod Biol,2006,16(5):123-135.
[5] Tayade C,Black G P,FANG Yuan,et al. Differential gene expression in endometrium, endometrial lymphocytes, and trophoblasts during successful and abortive embryo implantation[J].J Immunol,2006,176:148-156.
[6] Sherwin J R, Freeman T C, Stephens R J, et al. Identification of genes regulated by leukemia-inhibitory factor in the mouse uterus at the time of implantation[J]. Mol Endocrinol, 2004,18(9):2185-2195.
[7] Fouladi N A A, Andreu C V, Nijjar N, et al. Role of leukemia inhibitor factor (LIF) in decidualisation of murine uterine stromal cells in vitro[J]. J Endocrinol,2004,181(3):477-492.
[8]Perrier d'H S. Implantation: the first maternal-embryo crosstalk[J]. J Gynecol Obstet Biol Reprod (Paris) (in French),2004,33(1 Pt 2):S5-S8.
[9]Perrier d'H S, Charlet R C, Berndt S, et al. Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium[J]. Hum Reprod,2004,19(11):2633-2643.
[10]Rodriguez C I,Cheng JR-Gang,Liu Lin-Da, et al. Cochlin,a secreted von Willebrand factor type a domain-containing factor,is regulated by leukemia inhibitory factor in the uterus at the time of embryo implantation[J]. Endocrinology,2004,145(3):1410-1418.
[11]Aghajanova L,Altmae S,Bjuresten K,et al. Disturbances in the LIF pathway in the endometrium among women with unexplained infertility[J].Fertil Steril,2008,90(4): 1081-1086.
[2] Sherwin JR, Freeman TC, Stephens RJ, et al. Identification of genes regulated by leukemia-inhibitory factor in the mouse uterus at the time of implantation. Mol Endocrinol,2004,18(9):2185-2195.
[3] Kralickova M,Sima R,Vanecek T,et al. Leukemia inhibitory factor gene mutations in the population of infertile women are not restricted to nulligravid patients.Eur J Obstet Gynecol Reprod Biol,2006,16(5):123-135.
[4]武泽,任平,章晓梅,等.复发性流产和不明原因不孕患者子宫内膜白血病抑制因子表达研究.中国优生与遗传杂志,2005,13(6):16-18.
[5]张松灵,张晓霞,杨玉兰.白血病抑制因子在原发不孕症患者子宫内膜的表达.吉林大学学报(医学版),2003,29(5):643-644.
[6]李永丽,徐仙.LIF与种植窗期子宫内膜容受性,中国妇幼健康研究,2009,20(1):85-87.
[7]张亚红,徐仙,胡蓉,等.左右侧卵巢卵泡液中LIF与卵子质量关系的研究.中国计划生育学杂志,2010,20(6):96-97.
[8] Chen JR,Cheng JG,Shatzer T,et al.Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryo genesis.J Endocrinol, 2000,141(12):4365-4372.
[9] Aghajanova L.Leukemia inhibitory factor and human embryo implanta- tion. Ann NY Acad Sci,2004,103(4):176-183.
[10] Rungsiwiwut R,Rungarunlert S,Numchaisrika P,et al. Effect of leukemia inhibitory factor(LIF) on the quality of in vitro produced mouse blastocysts and subsequent derivation of embryonic stem (ES) cells.J Med Assoc Thai,2008, 9(1):608-614.
[11] D. Vogiagis, R. C. Fry, R. M. Sandeman et al.Leukaemia inhibitory factor in endometrium during the oestrous cycle,early pregnancy and in ovariectomized steroid-treated ewes.Journal of Reproduction and Fertility,1997,10(9),279-288.
[12] M. von.Wolff, C. J. Thaler, T.Strowitzky, et al. Regulated expression cytokines in endometrium throughout the mestrual cycle: dysregulation in habitual abortion.Molecular Human Reproduction,2000,6(7):627-634.
[13] D.B.Chen, R. Hilsenrath,Z.M.Yang,et al.Implantation: Leukaemia inhibitory factor in human endometrium during the menstrual cycle: cellular origin and action on production of glandular epithelial cell prostaglandin in vitro.Human Reproduction,1995,10(4):911-918.
[14] D Vogiagis,M M Marsh,R C Fry,et al.Leukaemia inhibitory factor in human endometrium throughout the menstrual cycle. Journal of Endocrinology, 1996, 148(1):95-102.
[15] Coskun S,Usumcu M,Jaroudi K,et al.Presence of leukemia inhibitory factor and interleukin-12 in human follicular fluid during fo11icular growth. Am J Reprod Immunol,1998,40(10):13-18.
[16] Janet E Hall,Corrine K.Weltand,Daniel W.Cramer.Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less use for at predicting outcome.Human ReProduction,1999,14(2):409-415.
[17] Hsieh YY,Chang CC,Tsai HD,et al.Leukemia inhibitory factor infollicular luid is not related to the number and quality of embryos as well as implantation and Pregnanty rates.Biochem Genet,2005,43(10):501-506.
[18]马小红,徐仙,胡蓉.卵巢对控制性超排卵反应的回顾性分析.中国妇幼健康研究,2008,19(3):216-218.
[19]赵海波,何亚绒,李爱莉,等.人卵泡液中白血病抑制因子浓度及其对卵母细胞发育的影响.第四军医大学学报,2004,25(6):554-556.
[20] Piccinni MP,Scaletti C,Maggi E,et al,Role of hormonecontrolled Th1-and Th2-type cytokines in successful pregnancy.J Neuro immunol,2000,109(1):30-33.
[21] Arici A,Engin O,Attar E,et al.Modulation of leukemia inhibitory factor gene expression and protein biosynthesis in human endometrium. J Clin Endocrinol Metab,1995,80(6):1908-1914.
[22] Hambartsoumian E,Taupin J L,Moreau J F,et al.In vivo administration of progesterone inhibits the secretion of endometrial leukemia inhibitory factor in vitro.Mol Hum Reprod,1998,4(11):1039-1044.
[23] K. Wanggren, P.G. Lalitkumar, F. Hambiliki,et al. Leukaemia inhibitory factor receptor and gp130 in the human Fallopian tube and endometrium before and after mifepristone treatment and in the human preimplantation embryo. Mol Hum Reprod,2007,13(6):391-397.
[24] Sengupta J,Dhawan L,Ghosh D. Immunohistochemical localization of leukemia inhibitory factor, interleukins 1 and 6 at the primary implantation site in the rhesus monkey.Cytokine,2003,24(6):277-285.
[25] Fouladi Nashta AA, Andreu CV, Nijjar N, et al. Role of leukemia inhibitor factor(LIF) in decidualisation of murine uterine stromal cells in vitro. J Endocrinol,2004,181(3):477-492.
[26] Sawai K, Matsuzaki N, Okada T, et al. Human decidual cell biosynthesis of leukaemia inhibitory factor: regulation by decidualcytokinesand steroid hormones.BiolReprod,1997,56(5):1274-1280.
[27]李永丽,徐仙,赵君利,等.体外受精-胚胎移植术移植日子宫内膜容受性的超声学研究.中国妇幼保健,2009,35(5):16-18.
[28]李路,徐步芳,陈秋菊,等.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.生殖与避孕,2008,28(2):89-94.
[29]李蓉,乔杰,王威,等.多囊卵巢综合征患者着床窗口期子宫内膜容受性的改变.中国优生与遗传杂志,2007,15(10):23-25.
[30]王琳,史常旭,常青,等.白血病抑制因子在子宫内膜异位症并发不孕患者黄体中期子宫内膜中的表达.生殖与避孕,2002,22(6):355-357.
[31] Yu Xiao, Xiao Sun, Xiuli Yang, et al. Leukemia inhibitory factor is dysregulated in the endometrium and uterine flushing fluid of patients with adenomyosis during implantation window.Ferti and Steri,2009,3(1):1-5.
[32] Mikolajczyk M,Skrzypczak J,Szymanowski K,et al.The assessment of LIF in uterine flushing-a possible new diagnostic tool in states of impaired fertility. Reprod Biol,2003,3(3):259-270.
[33] Tsai HD,Chang CC,H sieh YY,et al.Leukemia inhibitory factor expression in different endometrial locations between fertile and infertile women throughout different menstrual phases [J].Assist Reprod Genet,2000,17(8): 415-418.
[34]董方莉,谭丽,郑英.植入窗期血清孕激素水平及子宫内膜白血病抑制因子表达对体外受精-胚胎移植结局的预测价值.生殖医学杂志,2007,16(1):20- 23.
[35] Emily B. Cullinan, Susan J. Abbondanzo, Patrick S. Anderson, et al. Leukemia inhibitory factor(LIF) and LIF receptor expression in human endometrium suggests a potential autocrine/paracrine function in regulating embryo implantation. Acad Sci,1996,93(4):3115-3120.
[36] Jemma Evans,Rob D. Catalano,Pamela Brown,et al.Prokineticin 1 mediates fetal-maternal dialogue regulating endometrial leukemia inhibitory factor.THE FASEB J,2009,23(7):2165-2175.
[1]Aghajanova L. Leukemia inhibitory factor and human embryo implanta- tion[J]. Ann NY Acad Sci,2004,103(4):176-183.
[2] Guney M , Erdemoqlu E , Oral B , et al. Leukemia inhibitory factor (LIF) is immunohistochemically localized in tubal ectopic pregnancy[J].Acta Hostpcjem,2008,110(4): 319-323.
[3] DING Tian-bing,SONG Haengseok,WANG Xiao-hong,et al. Leukemia inhibitory factor ligand-receptor signaling is important for uterine receptivity and implantation in golden hamsters (Mesocricetus auratus)[J]. Reproduction,2008,135(1):41-53.
[4] Kralickova M,Sima R,Vanecek T,et al. Leukemia inhibitory factor gene mutations in the population of infertile women are not restricted to nulligravid patients [J]. Eur J Obstet Gynecol Reprod Biol,2006,16(5):123-135.
[5] Tayade C,Black G P,FANG Yuan,et al. Differential gene expression in endometrium, endometrial lymphocytes, and trophoblasts during successful and abortive embryo implantation[J].J Immunol,2006,176:148-156.
[6] Sherwin J R, Freeman T C, Stephens R J, et al. Identification of genes regulated by leukemia-inhibitory factor in the mouse uterus at the time of implantation[J]. Mol Endocrinol, 2004,18(9):2185-2195.
[7] Fouladi N A A, Andreu C V, Nijjar N, et al. Role of leukemia inhibitor factor (LIF) in decidualisation of murine uterine stromal cells in vitro[J]. J Endocrinol,2004,181(3):477-492.
[8]Perrier d'H S. Implantation: the first maternal-embryo crosstalk[J]. J Gynecol Obstet Biol Reprod (Paris) (in French),2004,33(1 Pt 2):S5-S8.
[9]Perrier d'H S, Charlet R C, Berndt S, et al. Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium[J]. Hum Reprod,2004,19(11):2633-2643.
[10]Rodriguez C I,Cheng JR-Gang,Liu Lin-Da, et al. Cochlin,a secreted von Willebrand factor type a domain-containing factor,is regulated by leukemia inhibitory factor in the uterus at the time of embryo implantation[J]. Endocrinology,2004,145(3):1410-1418.
[11]Aghajanova L,Altmae S,Bjuresten K,et al. Disturbances in the LIF pathway in the endometrium among women with unexplained infertility[J].Fertil Steril,2008,90(4): 1081-1086.