The Expression And Significance Of CD44v6, E-cadherin And Ang-1in Endometrium During The Window Of Implantation Of Polycystic Ovary Syndrome

Polycystic ovarian syndrome(PCOS) is a disease caused by reproductive endocrineand metabolic disorders in Women of childbearing age.Although the patient withdrug treatment returns to her normal ovulation and endocrine,she still has high rate ofabortion and low rate of pregnancy,which is possibly caused by long-term hormonalimbalance account for dropping endometrial receptivity. A large number of domesticand foreign Studies have shown that abnormal endometrial receptivity is caused byperennial Endocrine disorder of PCOS patients may be one reason for thisphenomenon.The successful embryo implantation requires not only a well-developed embryosand endometrial receptivity state,but also has close relationship with bothsynchronous development.The ability of accepting embryo implant endometrium iscalled the endometrial receptivity.The first20-24days of the menstrual cycle (6-10days after ovulation) during normal regular menstrual cycle are called "endometrialimplantation window period",only this period the embryo would be accepted byendometrial.In recent years,the implantation window of endometrial receptivitybecome the hot and difficult research of domestic and abroad.Numerous studies showthat hormones,genes,molecules etc,is closely related to endometrial receptivity.Current study found that matrix metalloproteinases,10homeobox gene,osteopontin, integrin etc are considered endometrial receptivity markers,but theystill can not fully explain and analyze the molecular mechanisms of uterinereceptivity established.CD44molecule is a cell surface transmembrane glycoprotein being a kind ofadhesion molecules.Its gene which is divided into standard CD44(eCD44s) andvariant eCD44(eCD44v) locates on the short arm of chromosome21.CD44moleculesmainly participate in the Specific adhesion process of cell-cell and cell-matrix.Inrecent years, many researches on the CD44molecule, particularly tumors: It hasroles of mediating lymphocyte shuttle and activating lymphocyte,and s closely relatedto the tumor differentiation, proliferation and metastasis.There are new studies foundthat CD44molecule is specifically expressed in the endometrium plays an importantrole in regulating the reproductive process.By the above inference that CD44molecule is a sign of the receptivity of endometrium markers,which may beinvolved in the process of embryo implantation.Angiopoietin (Angiopoietin Ang) family is a newly discovered kind of endothelialcell-specific angiogenic factor,Ang-1is a member of the the angiogenin family.Inrecent years, There are researchers found that Ang expressed in embryonic and adultvascular tissue,also expressed in a variety of pathological conditions of cancer,inflammation,trauma,etc.A mechanism of conglutination-invasion-blood vesselsformation is necessary for embryo implantation.The change of the endometrialmicroenvironment,which is changed by effects of Ang-1with extracellular matrix,isadvantageous to the blastocyst implantation.Numerous studies show that Ang-1maybe involved in the establishment of endometrial receptivity molecular mechanisms.Calcium binding protein (cadherin) is mainly mediates adhesion of the same typeof cells of specific organs and tissues.According to its basic features can be dividedinto classical cadherin,desmosomes cadherln,original cadherin-associated protein andother cadhetin four families.E-cadherin can mediated connection of epithelial cellsand occurrence and differentiation of organ, which belongs to the classicalcadherin.Some foreign scholars study showed E-cadherin expresses and cyclicallychanges in endometrial epithelium, and E-cadherin may be related to embryo implantation and trophoblast cells differentiation and occurrence.This issue will use the immunohistochemical S-P method to determine theexpressiones of CD44v6,E-cadherin and Ang-1in the endometrium of PCOS patientswith drug treatment returns to her normal ovulation and infertility patients with othercauses during the window of implantation,and discuss the possible reasons of PCOSpatients still appears the low pregnancy rate and high abortion rate after returns to hernormal ovulation and endocrine.objective1. Research the expression of CD44v6,E-cadherin and Ang-1in the endometrialtissues of experimental groups and control groups during the window of implantationand relations with the receptivity of endometrium2. Discuss relations between CD44v6,E-cadherin and Ang-1with PCOS patientsstill appears the low pregnancy rate and high abortion rate after returns to her normalovulation and endocrine.1. Object of studyExperimental group:married PCOS patients15cases considered experimentalgroup(By “Rotterdam standard diagnostic criteria”of2003)at the outpatient of theThird Affiliated Hospital of Zhengzhou University from August2012to February2013, aged23to35years,the average age (26.73±2.84)years.Meeting the followingconditions: patients returns to her normal ovulation and endocrine during treatment.or3to6months,menstrual becomes basically regulate,and normal ovulation in thenatural cycle or after ovulation induction treatment,and B-ultrasound by vaginaldidn’t find ovaries and uterine organic disease,and husband’s semen examinationdidn’t find abnormity.Control group:Infertile patients were induced on account of the husband’s orfallopian factors tubes18cases considered control group at the outpatient of the ThirdAffiliated Hospital of Zhengzhou University from August2012to February2013,aged23to35years,the average age(27±3.12)years.Meeting the followingconditions:Regular menstruation, ovulation, endocrine determination of normal,and For nearly three months not used hormone drugs,and no other internal medicinediseases and complications,and-ultrasound by vaginal didn’t find ovaries and uterineorganic disease.Two groups of samples have been carried out to collect after informed consent ofpatients and their families2. Specimen processing and testing methodsTransvaginal B ultrasound testing to determine the experimental group and thecontrol group with normal follicular development and ovulation during ovulatoryperiod. take fasting venous blood during8to11days after ovulation, and determineestrogen(E), progesterone(P)and human chorionic gonadotropin (HCG) levels. It isbelieved that pregnancy is impossible when the value of HCG <30IU/L.Taketissue using a one-time endometrial suction on the afternoon of the day confirmedfasting venous blood HCG <30IU/L with Patients’consent.Endometrial tissues werestained with HE, and its histologic staging is judged accordance with theNoyesstandards for histologic staging,and the expression of CD44v6,E-cadherin andAng-1were qualitative and determined semi-quantitatively detected byimmunohistochemistry method.3. Statistical analysisUsing statistical analysis SPSS17.0software, The quantitative data were analyzedby t test The qualitative datas are showed using Chi-square test and Fisher’s exactprobabilities.Correlation analysis ware used by the pearson correlation analysis,α=0.05as significant level.Results1. Comparison of general condition between the experimental group and controlgroup:Two groups of patients, the differences of the substructure level of endocrinesecretion,body mass index(BMI), their age and are all no statistically significant(P>0.05).2. Comparison of the serum E2and P level in the experimental group and controlgroup during window of implantation:The difference of serum E2level in two groups is no statistically significant(P>0.05).The difference of serum P level in two groupsis statistically significant(P <0.05).3. Comparison of endometrial thickness between the experimental group and controlgroup in the window of implantation:endometrial thickness in in the experimentalgroup was significantly lower than the control group,The difference of serum P levelin two groups is statistically significant(P <0.05).4. Expression of the CD44v6in the experimental group and control group duringwindow of implantation:CD44v6is mianly expressed in Cell membrane of Stromalcells and glandular epithelial cells in endometrial tissues of the experimental groupand the control group during the window of implantation. The Expression of theexperimental group is lower than in control group The difference is statisticallysignificant(P <0.05).5. Expression of the E-cadherin in the experimental group and control group duringwindow of implantation:E-cadherin is expressed in both two groups ofendometrium,Expression in the endometrial cytoplasm of glandular epithelial cells ofexperimental group during window of implantation is less than in control group,Thedifference is statistically significant(P <0.05).6. Expression of the Ang-1in the experimental group and control group duringwindow of implantation: Ang-1is mianly expressed in Cell membrane of Stromalcells and glandular epithelial cells in endometrial tissues of the experimental groupand the control group during the window of implantation. The Expression of theexperimental group is lower than in control group The difference is statisticallysignificant(P <0.05).7. The expression of CD44v6, Ang-1and E-cadherin in the endometrium of PCOSare positively correlated to each other(P <0.05).Conclusion1. the abnormal manifestation of endometrium CD44v6,E-cadherin and Ang-1whenthe patients of PCOS are in the implantation window period, which can results inlower endometrial receptivity. That’s one of the important reasons why the patients ofPCOS suffer adverse pregnancy outcomes, low rate of pregnancy and high rate of abortion.2. The expression of CD44v6, Ang-1and E-cadherin in the endometrium of PCOSare positively correlated to each other.It prompt that Collaboration of them lead toadverse pregnancy outcomes of PCOS patients was corrected.