Expression of α4β1 and αvβ3 integrins in the endometrium of women using the T200 copper intrauterine device

Objective: To investigate the expression of α4 and β3 integrin subunit levels in the endometrium of healthy women and copper intrauterine device (IUD) T200 users.Design: Case control study.Setting: An academic teaching hospital and a primary care clinic.Patient(s): Thirteen copper IUD users and 13 normal fertile women.Intervention(s): Timed endometrial biopsies during the mid-secretory phase (days 20 to 24).Main Outcome Measure(s): Histologic dating of endometrium and immunohistochemical staining intensity of α4 and β3, using the semiquantitative immunohistochemical score (HSCORE).Result(s): All endometrial biopsies consistent with menstrual dates were examined for integrin expression (β3 and α4). No difference in α4 integrin expression was found between IUD users and controls in both luminal and glandular epithelium. In fertile controls, αvβ3 staining was present in 100% and 38.4% of glandular and luminal epithelium, respectively. In contrast, only 61.5% of the IUD users had any αvβ3 staining in the glandular epithelium and only 53.9% in the luminal epithelium. The intensity of immunoreactivity between the two groups (mean HSCORE) did not differ significantly.Conclusion(s): Proportionately, significantly fewer women using copper IUD had positive αvβ3 immunoreactivity in the glandular epithelium of mid-secretory endometrium.     

Difference in alpha(v)beta3 integrin expression in endometrial stromal cell in subgroups of women with unexplained infertility

OBJECTIVE: The aim of the study was to evaluate the endometrial receptivity by using alpha(v)beta3 expression in the midsecretory phase in different endometrial compartments in women with unexplained infertility. STUDY DESIGN: A prospective controlled clinical trial in a setting of a university teaching hospital was performed. Thirty-three fertile and 33 infertile women were included in the study. Midluteal endometrial biopsies of the endometrium were carried out during the implantation window. Immunohistochemical staining was performed for the expression of alpha(v)beta3 in endometrial samples. Alpha(v)beta3 expression was measured using the HSCORE scoring system in the endometrial glandular and luminal epithelium and in the endometrial stroma. Serum levels of estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, prolactin, total testosterone and dehydroepiandrosterone sulphate were measured in the early follicular phase and in the midluteal phase. RESULTS: The average alpha(v)beta3 integrin expression at different sites of the endometrium was not different in the infertile and fertile controls. However, the stromal alpha(v)beta3 integrin was found to be expressed significantly less in a subgroup of women with lower than average alpha(v)beta3 integrin expression in luminal epithelium than in fertile controls and significantly more in a subgroup of women with higher than average alpha(v)beta3 integrin expression in luminal epithelium. There was no difference in stromal alpha(v)beta3 integrin expression in the lower or higher glandular alpha(v)beta3 integrin expression subgroups. CONCLUSIONS: Alpha(v)beta3 integrin expression in endometrial stromal cells may be different in subgroups of women with unexplained infertility.     

Alterations in expression of endometrial endothelial nitric oxide synthase and alpha(v)beta(3) integrin in women with endometriosis

OBJECTIVE: To determine the expression of endometrial endothelial nitric oxide synthase (eNOS) protein and alpha(v)beta(3) integrin in patients with and without endometriosis. DESIGN: Case-control cohort study. SETTING: University-based tertiary care center. PATIENT(S): Endometrial biopsy samples were obtained from 9 fertile women with regular cycles and 30 infertile women with varying severity of endometriosis. Peritoneal fluid levels of nitric oxide were determined in 13 infertile women with a normal pelvis and 12 infertile women with endometriosis. MAIN OUTCOME MEASURE(S): Expression of eNOS and alpha(v)beta(3) integrin protein in the endometrium and peritoneal fluid levels of nitric oxide. RESULTS: In patients with endometriosis, expression of eNOS was significantly increased in the glandular and luminal epithelium, with no significant changes in the stroma. Peritoneal fluid levels of nitric oxide were unchanged, and expression of alpha(v)beta(3) integrin expression in glandular and luminal epithelium was significantly decreased compared with controls. A significant negative correlation was observed between luminal expression of eNOS and alpha(v)beta(3) integrin and between glandular expression of eNOS and luminal expression of alpha(v)beta(3) integrin. CONCLUSION(S): The nitric oxide pathway may play a role in the pathogenesis of endometriosis.     

Expression of alpha6 and beta4 integrin subunits throughout the menstrual cycle: no correlation with uterine receptivity.

OBJECTIVE: To compare the expression of alpha6 and beta4 integrin subunit levels throughout the menstrual cycle in the endometrium of healthy women and infertile women. DESIGN: Prospective study. SETTING: An academic teaching hospital. PATIENT(S): Endometrium was collected from 58 women, including healthy subjects (n = 28) and patients undergoing diagnostic testing for infertility (n = 30). INTERVENTION(S): Endometrial biopsies were performed throughout the menstrual cycle in healthy women and infertile women. MAIN OUTCOME MEASURE(S): Immunohistochemical staining intensity of alpha6 and beta4 using the semiquantitative immunohistochemical score, compared using regression analysis and analysis of variance with Scheffé's correction. RESULT(S): There was no correlation between menstrual cycle phase and endometrial integrin subunit alpha6 or beta4 on glandular or luminal epithelium. Even women with identified luteal phase defects had indistinguishable patterns of expression for these integrin subunits during the window of implantation. CONCLUSION(S): The integrin subunits alpha6 and beta4 are expressed uniformly throughout the menstrual cycle on glandular and luminal epithelium. These integrins may have a housekeeping role in anchoring endometrial epithelium and do not appear to be useful markers of uterine receptivity.     

Differential expression of endometrial integrins and progesterone receptor during the window of implantation in normo-ovulatory women treated with clomiphene citrate

OBJECTIVE: To assess the effect of clomiphene citrate (CC) on endometrial epithelial integrins and P receptors (PR) during the window of implantation. DESIGN: Controlled, prospective, clinical study. SETTING: Teaching hospital and university research laboratory. PATIENT(S): Thirty-one fertile, normo-ovulatory women participated in this trial. Thirteen women exhibited a CC-stimulated cycle with 50 mg on days 5-9, and 18 women with spontaneous menstrual cycles served as controls. INTERVENTION(S): Endometrial biopsies in the midluteal phase. MAIN OUTCOME MEASURE(S): Immunohistochemical determination and endometrial cellular localization of alpha1, alpha v, beta3, and alpha4 epithelial integrins and PR during the window of implantation. The staining intensity was assessed by a semiquantitative index (HSCORE) and compared by nonparametric Mann-Whitney test. RESULT(S): Higher plasma levels of P and E2 and delayed histologic dating of the endometrium (38%) were features of CC-treated women. In addition, a low epithelial beta3 integrin expression and persistent PR were observed in glandular epithelial cells of "out-of-phase" endometrial biopsies from CC-treated women. In contrast, in "in-phase" biopsies, neither epithelial PR nor beta3 integrin were different from spontaneous control cycles. There was no difference in the expression of alpha1, alpha v, and alpha4 between the groups studied. CONCLUSION(S): The administration of clomiphene produces aberrant endometrial beta3 integrin expression in conjunction with a failure in the down-regulation of PR during the window of implantation in a significant number of normo-ovulatory women, notwithstanding the higher plasma P levels. Therefore, CC might affect the expression of endometrial receptivity markers.     

Endometrial integrin expression in women undergoing in vitro fertilization and the association with subsequent treatment outcome

OBJECTIVE: To study the endometrial expression of three integrins (alpha v beta 3, alpha 4 beta 1, and alpha 1 beta 1) in women undergoing IVF-intracytoplasmic sperm injection (ICSI) treatment and assess whether they could be used to predict subsequent treatment success.Prospective observational study.Healthy volunteers in a large teaching hospital. PATIENT(S): Sixty-six patients attending for IVF-ICSI treatment. INTERVENTION(S): Timed endometrial biopsies were taken, during the implantation window at LH + 7-9 days, from women before IVF-ICSI treatment. MAIN OUTCOME MEASURE(S): Histological dating of endometrium and immunohistochemical staining intensity of alpha 4 beta 1, alpha v beta 3, and alpha 1 beta 1 integrins. The integrin levels were correlated with subsequent success rates. RESULT(S): There was a statistically significantly greater expression of alpha v beta 3 in the luminal epithelium of those patients who had successful treatment. However, treatment was successful in some patients with negative expression. CONCLUSION(S): Integrins are important markers of endometrial receptivity. There is an association between an in-phase endometrial biopsy, with positive luminal alpha v beta 3 integrin expression, and subsequent treatment success. However, the clinical value of assessing the endometrium before treatment has drawbacks, and further work needs to be done before this can be considered a clinically useful test.     

Different types of recurrent miscarriage are associated with varying patterns of adhesion molecule expression in endometrium

This study investigated the hypothesis that different types of recurrent miscarriage history are associated with different markers of endometrial receptivity. A secondary objective was to compare the distribution in endometrial epithelium of a group of cell surface components with roles in cell adhesion. Of 54 women who had an implantation window endometrial biopsy, 17 had idiopathic recurrent fetal loss, 17 had idiopathic recurrent loss of empty gestation sacs, 10 had recurrent implantation failure and 10 had two or more normal pregnancies. Immunohistochemistry and HSCORE was used with frozen sections for integrins (alpha1beta1, alpha4beta1, alpha(v)beta3), and MUC1 (BC2) and paraffin sections for osteopontin and MUC1 (BC3). Epithelial beta1 integrins were located primarily in the basolateral membrane compartment. Consistently greater expression of alpha4beta1, alpha1beta1 and alpha(v)beta3 was seen in the luminal epithelium and greater expression of alpha4beta1 and alpha1beta1 in the glandular epithelium of women with recurrent fetal loss when compared with those with recurrent loss of empty gestation sacs. There were no significant differences in the expression of osteopontin or MUC1 between groups. Different endometrial integrin distribution was found in women suffering different types of recurrent pregnancy loss. It is postulated that impairment of the implantation barrier contributes to recurrent fetal loss.     

Expression of alpha(v)beta3 and alpha4beta1 integrins throughout the putative window of implantation in a cohort of healthy fertile women

BACKGROUND: Blastocyst implantation is a dynamic process requiring a specific cascade of cellular interactions and endometrial changes. The aim of this prospective observational study was to investigate the endometrial expression of alpha(v)beta3 and alpha4beta1 integrins throughout the window of implantation in healthy fertile women. MATERIALS AND METHODS: Forty fertile women (mean age 29.7 +/- 6.2 years) were recruited for this study. All underwent two endometrial biopsies in a single menstrual cycle. The first biopsy was performed on postovulatory day 6, while the second was taken on postovulatory day 8. Histological dating and immunohistochemical assessments of alpha(v)beta3 and alpha4beta1 integrins were analyzed. Oestradiol and progesterone serum concentrations were also measured at the time of biopsy. RESULTS: Second endometrial biopsy could not be performed in two of the 40 women (5%) because their menses had started in advance. No inflammatory or reactive phenomena were observed after biopsy. All the samples showed an in-phase endometrium. alpha(v)beta3 integrin expression was found in 21 out of the 38 first biopsies and in all 38 second biopsies (55.2% vs. 100%, p < 0.001). alpha4beta1 integrin expression was not significantly different between first and second biopsies (68.4% and 76.3%, NS). Oestradiol and progesterone serum concentrations were similar throughout the implantation window. Twelve of the 38 women (31.6%) conceived within 12 months of completing the study. All these had significantly higher alpha(v)beta3 integrin expressions in mid-luteal phase biopsies compared with those who did not conceive. CONCLUSIONS: These immunohistochemical findings demonstrate that both alpha(v)beta3 and alpha4beta1 integrins have a spatial and temporal expression throughout the implantation window in the endometrium of fertile women. Moreover, the shortage of alpha(v)beta3 integrin expression during the mid-luteal phase results in a detrimental effect for blastocyst implantation.     

A preliminary study comparing the endometrial expression of inhibin, activin and follistatin in women with a history of implantation failure after IVF treatment and a control group

The aim of this study was to evaluate the expression of activin: beta A and beta B subunit and follistatin in endometrium of women with implantation failure ( n = 10) and compare it with a fertile control group ( n = 7). Immunohistochemical staining intensity for follistatin in the endometrial glandular epithelium from women with implantation failure were significantly lower than that in control women ( P = 0.03). The decreased expression of follistatin in epithelial cells in the endometrium of women with implantation failure after in vitro fertilisation (IVF) may suggest that follistatin may play a role in the implantation process.     

Use of integrins to date the endometrium

OBJECTIVE: To compare traditional histologic dating criteria of the endometrium with immunohistochemical criteria based on epithelial integrin expression during the menstrual cycle. DESIGN: Prospective clinical study. SETTING: An academic teaching hospital. PATIENT(s): Fertile and infertile women undergoing endometrial biopsy. MAIN OUTCOME MEASURE(s): Immunohistochemical staining intensity and distribution (HSCORE) of three integrins and traditional histologic endometrial dating. RESULT(s): In 1,501 endometrial specimens, phase assignment-based integrin staining was 95% and 85% concordant with histology for the proliferative and early secretory phase, respectively, but only 54% and 49% concordant for the middle and late secretory phase, respectively. The greatest disagreement occurred during the midluteal phase. Of 1,090 patients who underwent sampling 6-10 days after detection of a urinary LH surge (corresponding to cycle days 20-24), multiple logistic regression analysis revealed that endometriosis was positively correlated and male factor infertility was negatively correlated with absent beta3 integrin subunit expression. Diagnosis and absent epithelial alpha4beta1 expression were not related. Patient age was not correlated with the incidence of abnormalities in integrin expression. CONCLUSION(s): Traditional histologic dating of the endometrium has remained the gold standard for nearly 50 years. Although the use of marker proteins provides additional information and may reflect endometrial function or receptivity, such markers cannot yet replace traditional methods of endometrial assessment.     

High frequency of iatrogenic monozygotic twins with administration of clomiphene citrate and a change in chorionicity

Immunostaining intensity for alpha(1), alpha(4), alpha(v)beta(3), and beta(3) was assessed by H score in timed peri-implantation endometrium from 21 women with unexplained recurrent miscarriage and 16 healthy fertile women. No significant difference in H scores in gland epithelium, luminal epithelium, stroma, or blood vessels was observed between the two groups, suggesting that alpha(1), alpha(4), alpha(v)beta(3) and beta(3) integrins are expressed normally in the endometrium of women with unexplained recurrent miscarriage.     

Endometrial dating and determination of the window of implantation in healthy fertile women

OBJECTIVE: To reassess endometrial morphological criteria of normality identifying the best morphological and molecular "implantation window" indicators in normal women. DESIGN: Prospective clinical study.Setting: Assisted reproductive unit. PATIENT(s): Fourteen healthy volunteers. INTERVENTION(s): Blood sampling for LH, E(2), and progesterone (P4) determinations. Daily vaginal ultrasounds. Two endometrial biopsies per volunteer, 7 days apart, during luteal phase. MAIN OUTCOME MEASURE(s): Endometrial dating, pinopodes formation, immunohistochemical determination of integrins (alphavbeta3, alpha4beta1), leukemia inhibitory factor (LIF), interleukin-1 receptor type I (IL-1R tI), mouse ascites Golgi (MAG), the transmembrane mucin (MUC-1), and P4 receptor expression. RESULT(s): In 26 of 28 biopsies observers agreed; in two biopsies there was a discrepancy (difference of 72 hours). With use of LH peak, 24 of 26 samples were in phase, and 2 were 3 days behind. Pinopodes appeared on days 20-21 and persisted through day 28 in small groups or larger areas. beta3 Integrin was highly expressed in luminal and glandular epithelium from day 22 through 28; 48 hours thereafter pinopodes appeared. alpha4 Subunit exhibited luminal epithelium reaction positivity on days 22-23 and glands on days 18-23. LIF and IL-1R tI showed weak, erratic expression. MAG antibodies showed luminal epithelium expression up to day 22 and glands up to day 25. MUC-1 showed positivity during the whole luteal phase. P4 receptors were positive through day 20 and at the end of the luteal phase. CONCLUSION(s): The three most cited markers that frame the window of implantation do not correlate in our material. Pinopodes are present from day 20 on; beta3 and alpha4 integrin subunits indicate a window opening on days 22-23.     

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.     

Interleukin-11, IL-11 receptoralpha and leukemia inhibitory factor are dysregulated in endometrium of infertile women with endometriosis during the implantation window

Interleukin (IL)-11 is essential for embryo implantation in the mouse and evidence suggests it has a role in implantation in humans. This study has evaluated immunoreactive IL-11, IL-11 receptor (R) alpha and leukemia inhibitory factor (LIF) in endometrium of infertile women with endometriosis (I/E) and normal fertile women (controls) during the implantation window. Endometrial biopsies from I/E (N = 7) were timed from the LH surge and were post-ovulatory days (POD) 5-10. Control biopsies (N = 8) from women were between days 19 and 24 of the menstrual cycle. Staining intensity of IL-11, IL-11Ralpha and LIF evaluated using semi-quantitative immunohistochemistry scores. Immunoreactive IL-11, IL-11Ralpha and LIF were present predominantly in glandular epithelium, while luminal epithelium showed patchy staining. All controls stained positively for IL-11, IL-11Ralpha and LIF in glandular epithelium. IL-11 and IL-11Ralpha staining was absent from glandular epithelium in cohorts of I/E. LIF staining intensity in glandular epithelium was significantly lower in I/E compared to controls. The results suggest that reduced endometrial IL-11 and/or LIF may contribute to infertility in some endometriotic women.     

自然及促排卵周期子宫内膜整合素α4β1的表达

目的 了解氯米芬（CC）、绝经期促性腺激素（hMG）对黄体中期子宫内膜整合素α4β1表达的影响。方法 应用单克隆抗体,采用免疫组织化学技术检测48例正常妇女自然周期以及48例正常妇女、30例多囊卵巢综合征患者应用CC／绒毛膜促性腺激素（hCG）及CC／hMG/hCG方案促卵治疗后黄体中期子宫内膜整合素α4β1的表达。结果 子宫内膜整合素α4β1在正常妇女自然周期着床窗口期呈现强阳性表达,而CC、hMG抑制整合率α4β1的表达,两者比较,差异有极显著性（P＜0．01）;妊娠者较妊娠者整合素α4β1表达强度高。结论 促排卵周期黄体中期整合素α4β1表达下降或缺失,子宫内膜容受性下降,妊娠率降低。     

Lectin binding of endometrium in women with unexplained infertility

OBJECTIVE: To investigate whether peri-implantation phase endometrium in women with unexplained infertility differs from the endometrium of normal fertile women. DESIGN: Assessment of the function of the endometrium by using endometrial biopsy specimens and lectin histochemistry. SETTING: Infertility Clinic, Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen normal fertile women (group I) and 18 women with unexplained infertility (group II). INTERVENTIONS: Endometrial biopsies were obtained from both groups at 5, 7, and 9 days after the luteinizing hormone (LH) surge. MAIN OUTCOME MEASURES: Five biotinylated lectins, concanavalin A (ConA), wheat germ agglutinin (WGA), soybean agglutinin, Peanut, and Ulex europaeus I were used as analytical probes to study endometrial glycoconjugates. Histochemical staining was performed using the avidin-biotin peroxidase method. The lectin binding by endometrial glands, surface epithelium, stromal cells, and vessels was assessed. RESULTS: In group I, ConA stained the subnuclear glandular cytoplasm, glandular lumen, stroma cells, and surface epithelium. In group II, ConA binding to glandular or surface epithelium was none or equivocal. In group I, WGA bound to glandular cytoplasm and stroma cells on days LH + 5 and LH + 7. In group II, WGA binding was absent in glands but present in stroma. CONCLUSIONS: Reproductive failure of women with unexplained infertility may be associated with defective biosynthesis and distribution of glycoconjugates that subsequently results in an unfavorable endometrial environment during the peri-implantation phase.     

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.     

Xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis

OBJECTIVE: To investigate the expression of xanthine oxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of xanthine oxidase in endometrial tissues by using polyclonal antibody. SETTING: University hospital. PATIENT(S): Thirty-four women with endometriosis, 34 women with adenomyosis, and 44 fertile control women. INTERVENTION(S): Biopsy samples were obtained from the endometrium throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining (evaluation nomogram) score of endometrial cells. RESULT(S): The level of xanthine oxidase expression in the glandular epithelium of control varied according to menstrual phase, but no such variation in expression was seen in endometriosis. Variation in xanthine oxidase expression was observed during the menstrual cycle in patients with adenomyosis; this variation differed completely from that in controls. Xanthine oxidase expression was found in ectopic endometrial tissue in all cases. The mean evaluation nomogram levels in the glandular epithelium in adenomyosis tissue were as high as those in the early secretory phase in the eutopic endometrium. CONCLUSION(S): Aberrant expression of xanthine oxidase in eutopic and ectopic endometrium appears to play a pathologic role in endometriosis and adenomyosis.     

Distribution of cyclooxygenase-1, cyclooxygenase-2, and cytosolic phospholipase A2 in the luteal phase human endometrium and ovary

OBJECTIVE: To identify the distribution of the enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A(2) (cPLA(2)) in the human ovary and endometrium. DESIGN: Prospective clinical study. SETTING: Hospital-based unit for reproductive health and research laboratories. PATIENT(S): Twenty-nine healthy fertile women with normal menstrual cycles. INTERVENTION(S): Endometrial and ovarian biopsy samples were obtained from healthy, fertile women in the luteal phase of the menstrual cycle or during caesarean section. MAIN OUTCOME MEASURE(S): Pinopode formation and immunohistochemical staining of cPLA(2), COX-1, and COX-2. RESULT(S): In the endometrium, the immunostaining of cPLA(2) was most intense in the luminal epithelium when pinopodes were present. The staining of both COX-1 and COX-2 was most intense in the epithelial cells, with the stroma staining positive only for COX-2. The endometrial vessels expressed COX-2 but not COX-1. The staining of COX-1 and COX-2 was intense on the surface epithelial cells on the outer lining of the ovary. CONCLUSION(S): This study details the distribution of these prostaglandin synthase enzymes and emphasizes their importance for the functions of both the endometrium and the ovary.     

整合素β3及骨桥蛋白在子宫腺肌病患者子宫内膜中的表达及其意义

目的 探讨整合素β3及骨桥蛋白(OPN)在子宫腺肌病患者在位及异位子宫内膜中的表达及意义.方法 选择2007年1月-2008年7月于北京大学第一医院妇产科因子宫腺肌病行子宫全切除术的子宫腺肌病患者43例,收集其在位子宫内膜(在位内膜组),其中增殖期内膜11例,分泌期内膜32例(其中18例为分泌期中期);同时收集其异位子宫内膜(异位内膜组).选择同期因宫颈上皮内瘤变(CIN)Ⅱ～Ⅲ级或单纯浆膜下子宫肌瘤行子宫全切除术的患者41例为对照组,收集其子宫内膜,其中增殖期内膜12例,分泌期内膜29例(其中19例为分泌期中期).采用免疫组化法和实时荧光定量PCR技术检测各组患者子宫内膜中整合素β3和OPN的蛋白及mRNA表达.结果 (1)整合素β3和OPN蛋白主要表达于在位和异位子宫内膜的腺体.子宫内膜中整合素β3和OPN蛋白的表达水平,在位内膜组、异位内膜组、对照组分别为1.6±0.8和1.7±0.7、1.7±0.7和1.8±0.9、2.1±0.9和2.0±0.9,各组之间分别比较,差异均有统计学意义(P<0.05).在位内膜组增殖期子宫内膜中整合素β3和OPN蛋白的表达水平分别为0.8±0.4和0.7±0.3,均低于分泌期(分别为1.8±0.8和1.9±0.8),差异均有统计学意义(P<0.01);对照组增殖期子宫内膜中整合素β3和OPN蛋白的表达水平分别为1.0±0.4和1.0±0.4,也均低于分泌期(分别为2.5±0.7和2.5±0.7),差异也均有统计学意义(P=0.000).在位内膜组分泌期中期子宫内膜中整合素β3和OPN蛋白的表达水平分别为2.0±0.9和2.1±0.8,均低于对照组(分别为2.7±0.5和2.7±0.7),差异均有统计学意义(P<0.01).(2)子宫内膜中整合素β3和OPN mRNA的表达水平(以中位数表示),在位内膜组(分别为4.69和4.23)均低于异位内膜组(分别为7.96和14.84)和对照组(分别为13.47和17.40),差异均有统计学意义(P<0.05).在位内膜组增殖期子宫内膜中整合素β3和OPN mRNA的表达水平(分别为2.69和3.30)均低于分泌期(分别为5.54和11.40),差异均有统计学意义(P<0.01);对照组增殖期子宫内膜中整合素β3和OPN mRNA的表达水平(分别为3.12和4.75)也均低于分泌期(分别为19.94和21.00),差异也均有统计学意义(P=0.000);在位内膜组分泌期中期子宫内膜中整合素β3和OPN mRNA的表达水平(分别为10.10和14.34)均低于对照组(分别为21.50和24.18),差异均有统计学意义(P<0.05).结论 整合素β3和OPN在子宫腺肌病患者异位内膜的侵袭和生长过程中起着一定的作用,可能影响子宫腺肌病患者的胚胎着床.