种植窗期人子宫内膜LIF及整合素α_vβ_3的表达与胚胎种植成功率关系的研究
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摘要
目的:研究白血病抑制因子(LIF)与整合素αvβ3(Integrinαvβ3)在子宫内膜的表达,探讨LIF与整合素αvβ3与人胚胎种植的相关性。
方法:对42例拟行IVF-ET的妇女(其中原发不孕15例,继发不孕27例)在IVF-ET前一周期的黄体中期取子宫内膜,采用免疫组化SP法检测LIF和整合素αvβ3在患者子宫内膜中的表达,并用组织学积分H-score法对LIF和整合素αvβ3在种植窗期子宫内膜上皮中的表达进行定位和半定量分析。按经IVF-ET后治疗是否妊娠将42例不孕患者分为2组:妊娠组和非妊娠组。研究LIF和整合素αvβ3在子宫内膜上的表达与种植窗期子宫内膜容受性的相关性以及与IVF-ET结局的关系。
结果:1.LIF阳性表达定位于分泌期中期子宫内膜腔上皮细胞和腺上皮细胞的胞浆。妊娠组子宫内膜腔上皮细胞和腺上皮细胞LIF免疫组化H-Score积分值较未妊娠组高,差异有统计学意义(P＜0.05);
2.Integrinαvβ3阳性表达定位于分泌期中期子宫内膜腔上皮细胞和腺上皮细胞的胞浆。妊娠组子宫内膜腔上皮细胞和腺上皮细胞Integrinαvβ3免疫组化H-Score积分值较未妊娠组高,差异有统计学意义(P＜0.01);
3.分泌中期LIF和Integrinαvβ3在子宫内膜上皮细胞的表达妊娠组中的阳性率与非妊娠组中相比,经统计学分析有差异(P＜0.05)。
结论:
1.LIF和Integrinαvβ3的确表达于子宫内膜发育的特定时期——排卵后D7,也就是胚胎种植窗期。
2.妊娠组子宫内膜上皮LIF和Integrinαvβ3免疫组化H-score积分值高于未妊娠组,有统计学意义,暗示LIF和Integrinαvβ3对于子宫内膜的种植窗期的形成非常重要。
3.LIF和Integrinαvβ3在分泌中期子宫内膜上的高表达可以作为预测子宫内膜容受性的指标之一。
Objective:To determine the expressions of the endometrial leukemia inhibitory factor(LIF)and Integrinανβзin the endometrium and their correlation with the embryo implantation.
Methods:The endometrium samples were obtained during the implantation window from 42 patients undergoing IVF-ET.The endometrial LIF and Integrinανβзwere detected by immunohistochemistry using polyclonal antibody and semi-quantified by H-score.The 42 patients were divided into two groups according to the clinical outcomes:the pregnancy group(14 patients)and non-pregnancy group(28 patients). The expression of endometrial leukemia inhibitory factor(LIF)and Integrinανβзin the endometrium was studied and their relationship with Embryo Implantation outcome was investigated.
Results:
1.The LIF expresses in the cytoplasm of the luminal epithelial and glandular cells during the mid-stage of secretion.The H-scores from LIF immunostaining of luminal epithelial and glandular were significantly higher in the pregnant group than those in the non-pregnant group with statistical significance(P＜0.05).
2.Integrinανβзexpresses in the the luminal epithelial and glandular cells during the mid-stage of secretion.The H-scores from Integrinανβзimmunostaining of luminal epithelial and glandular were significantly higher in the pregnant group than those in non-pregnant group with statistical significance(P＜0.01).
3.Statistical difference(P＜0.05)was observed between the pregnant and the nonpregnant groups in the positive rates of the expression of LIF and Integrinανβзin the endometrium during the mid-stage of the secretion.
Conclusions:
1.LIF and Integrinανβзwas expressed in a specific stage of endometrial development,that is,the seventh day after ovulation,which is the embryo implantation window.
2.The H-scores from LIF and Integrinανβзimmunostaining of endometrium epithelial were significantly higher in the pregnancy group than those in the nonpregnancy group,indicating that LIF and Integrinανβзare important for the formation of the implantation window of the endometrium.
3.The enhanced expression of LIF and Integrinανβзin the endometrium during the mid-stage of the secretion can be employed as one of the criteria to predict the receptivity of the endometrium.
方法:对42例拟行IVF-ET的妇女(其中原发不孕15例,继发不孕27例)在IVF-ET前一周期的黄体中期取子宫内膜,采用免疫组化SP法检测LIF和整合素αvβ3在患者子宫内膜中的表达,并用组织学积分H-score法对LIF和整合素αvβ3在种植窗期子宫内膜上皮中的表达进行定位和半定量分析。按经IVF-ET后治疗是否妊娠将42例不孕患者分为2组:妊娠组和非妊娠组。研究LIF和整合素αvβ3在子宫内膜上的表达与种植窗期子宫内膜容受性的相关性以及与IVF-ET结局的关系。
结果:1.LIF阳性表达定位于分泌期中期子宫内膜腔上皮细胞和腺上皮细胞的胞浆。妊娠组子宫内膜腔上皮细胞和腺上皮细胞LIF免疫组化H-Score积分值较未妊娠组高,差异有统计学意义(P＜0.05);
2.Integrinαvβ3阳性表达定位于分泌期中期子宫内膜腔上皮细胞和腺上皮细胞的胞浆。妊娠组子宫内膜腔上皮细胞和腺上皮细胞Integrinαvβ3免疫组化H-Score积分值较未妊娠组高,差异有统计学意义(P＜0.01);
3.分泌中期LIF和Integrinαvβ3在子宫内膜上皮细胞的表达妊娠组中的阳性率与非妊娠组中相比,经统计学分析有差异(P＜0.05)。
结论:
1.LIF和Integrinαvβ3的确表达于子宫内膜发育的特定时期——排卵后D7,也就是胚胎种植窗期。
2.妊娠组子宫内膜上皮LIF和Integrinαvβ3免疫组化H-score积分值高于未妊娠组,有统计学意义,暗示LIF和Integrinαvβ3对于子宫内膜的种植窗期的形成非常重要。
3.LIF和Integrinαvβ3在分泌中期子宫内膜上的高表达可以作为预测子宫内膜容受性的指标之一。
Objective:To determine the expressions of the endometrial leukemia inhibitory factor(LIF)and Integrinανβзin the endometrium and their correlation with the embryo implantation.
Methods:The endometrium samples were obtained during the implantation window from 42 patients undergoing IVF-ET.The endometrial LIF and Integrinανβзwere detected by immunohistochemistry using polyclonal antibody and semi-quantified by H-score.The 42 patients were divided into two groups according to the clinical outcomes:the pregnancy group(14 patients)and non-pregnancy group(28 patients). The expression of endometrial leukemia inhibitory factor(LIF)and Integrinανβзin the endometrium was studied and their relationship with Embryo Implantation outcome was investigated.
Results:
1.The LIF expresses in the cytoplasm of the luminal epithelial and glandular cells during the mid-stage of secretion.The H-scores from LIF immunostaining of luminal epithelial and glandular were significantly higher in the pregnant group than those in the non-pregnant group with statistical significance(P＜0.05).
2.Integrinανβзexpresses in the the luminal epithelial and glandular cells during the mid-stage of secretion.The H-scores from Integrinανβзimmunostaining of luminal epithelial and glandular were significantly higher in the pregnant group than those in non-pregnant group with statistical significance(P＜0.01).
3.Statistical difference(P＜0.05)was observed between the pregnant and the nonpregnant groups in the positive rates of the expression of LIF and Integrinανβзin the endometrium during the mid-stage of the secretion.
Conclusions:
1.LIF and Integrinανβзwas expressed in a specific stage of endometrial development,that is,the seventh day after ovulation,which is the embryo implantation window.
2.The H-scores from LIF and Integrinανβзimmunostaining of endometrium epithelial were significantly higher in the pregnancy group than those in the nonpregnancy group,indicating that LIF and Integrinανβзare important for the formation of the implantation window of the endometrium.
3.The enhanced expression of LIF and Integrinανβзin the endometrium during the mid-stage of the secretion can be employed as one of the criteria to predict the receptivity of the endometrium.
引文
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[3]Paulson R J,et al.Embryo implantation after human in vitro fertilization:importance of endometrial receptivity.Fertil Steril 1990,53(5):870-874.
[4]Taylor E,Gomel V.The uterus and fertility.Fertil Steril.2008,89(1):1-16.
[5]Yu Ng EH,YeungWS,Yee Lan Lau E,et al.High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles[J].Hum Reprod,2000;15(2):250-255.
[6]Blazar A S.Hogan J W.et al.The impact of hydrosalpinx on successful pregnancy in tubal factor infertility treated by in vitro fertilization.Fertil Steril.1997;67:517-520.
[7]Noyes R W,Hertig A T,Rock J.Dating the endometrial biopsy.Fertil Steril 1950,1:3-25.
[8]Perrier d'Hauterive S,Charlet-Renard 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.Hum Reprod,2004,19(11):2633-2643.
[9]Daftary G S.Taylor H S.Molecular markers of implantation:clinical implications.Current Opinion in Obstetrics and Gynecology 2001,13(3):269-274.
[10]Lusine Aghajanova.Leukemia Inhibitory Factor and Human Embryo Implantation.Ann.N.Y.Acad.Sci.2004,1034:176-183.
[11]Lessey BA,et al.Luminal and Glandular Endometrial Epithelium Express Integrins Differentially Throughout the Menstrual Cycle:Implications for Implantation,Contraception,and Infertility.AJRI 1996;35(3):195-204
[12]Arnaout,M.Amin.Integrin structure:new twists and turns in dynamic cell adhesion[J].Immunological Reviews,2002,186(1):125-140.
[13]Lessey BA.Endometrial integrins and the establishment of uterine receptivity.Hum Reprod.1998.Volume 13 Supplement 3.
[14]Illera MJ,Cullinan E,Gui Y,et al.Blockade of the alpha(v)beta(3)integrin adversely affects implantation in the mouse.Biol Reprod,2000,62(5):1285-1290.
[15]Illera MJ,Lorenzo PL,Gui YT,et al.A role for alphavbeta-3 integrin during implantation in the rabbit model.Biol Reprod,2003,68(3):766-771
[16]Lessy BA.Implantation defects in infertile woman with endometriosis.Ann N YAcad Sci,2002,955:265-280.
[17]孔北华。女性生殖系统生理∥乐杰。妇产科学。6版。北京:人民卫生出版社,2004;23。
[18]庄广伦主编.现代辅助生育技术.北京:人民卫生出版社,2004.240
[19]Debra A.Budwit-Novotny,Kenneth S.et,al Immunohistochemical Analyses of Estrogen Receptor in Endometrial Adenocarcinoma Using a Monoclonal Antibody.Canser Research,1986,46:5419-5425.
[20]Finn C A,Lawn M A.A morphological analysis of the early implantation stages in the rat.Am J Anat 1967;120:185-226
[21]Enders AC,schlafke S Cytological aspecta of trophoblastuterine interaction in early implanation.Am J Anat 1969;125(1):1-29.
[22]Chaouat G,Dubanchet S,et al.Cytokines:Important for implantation?J Assist Reprod Genet.2007 Nov;24(11):491-505.Epub 2007 Nov 28.
[23]Zvonic S.Baugh JE,Arbour-Reily P,et al.Cross-talk among gp130 Cytokines in adipocytes[J].Biochem Mol Biol,2005,280(40):33856-33863.
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