Expression of alpha4beta1 and alphavbeta3 integrins in the endometrium of women using the T200 copper intrauterine device

OBJECTIVE: To investigate the expression of alpha4 and beta3 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 alpha4 and beta3, using the semiquantitative immunohistochemical score (HSCORE). RESULT(S): All endometrial biopsies consistent with menstrual dates were examined for integrin expression (beta3 and alpha4). No difference in alpha4 integrin expression was found between IUD users and controls in both luminal and glandular epithelium. In fertile controls, alphavbeta3 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 alphavbeta3 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 alphavbeta3 immunoreactivity in the glandular epithelium of mid-secretory endometrium.     

Changes in copper and zinc serum levels in women wearing a copper TCu-380A intrauterine device

Abstract

Objective To assess the effects of the copper intrauterine device (IUD) TCu-380A, on copper and zinc serum levels.

Material and methods This longitudinal study enrolled 121 women attending Health Centres in Tehran between November 2011 and August 2012. A blood sample was obtained before use and three months after insertion of a TCu-380A IUD. Serum levels of copper and zinc were measured for the 101 women who had completed three months with the device in situ. Analyses of change included paired t-tests, McNemar tests and linear regression.

Results Significant elevations in mean serum levels were found for both copper (170.22 μg/dl at three months vs.160.40 μg/dl at baseline, p = 0.034) and zinc (107.67 μg/dl at three months vs. 94.61 μg/dl at baseline, p < 0.001) three months after IUD insertion.

Conclusions A slight, but significant increase in copper serum levels, not reaching toxic levels, was observed three months after TCu-380A IUD insertion. Zinc levels too had risen significantly, which was quite unexpected, and warrants further investigation.     

A study of the copper T intrauterine contraceptive device (TCu 200) in nulliparous women

A study of the effectiveness and complications associated with the Model 200 copper T intrauterine device in 471 nulliparous women ranging in age from 14-33 years is reported, including 6044 woman-months of device use. 128 of the patients had had 1 or more previous abortions. This T-shaped device is made of polyethylene impregnated with barium sulfate, wound with .2 mm diameter copper wire providing a copper surface area of 200 square mm, and is inserted easily without anesthesia and with minimal pain. Continuation and failure rates were calculated for the first 12 months of use by life-table analysis. The overall continuation rate of device use was 74.2 per 100 women, the expulsion rate was 5.4, removal rate for bleeding or pain was 10.7, and pregnancy failure occurred at a rate of 1.7 per 100 women per year. These discontinuation event rates are lower than those reported for other IUDs in nulliparous women and comparable to IUD rates in multiparas. In the past, other IUD designs have been very unsatisfactory in nulliparas because of high expulsion and removal rates, but this study indicates that the TCu 200 IUD model is well accepted by nulliparas with good safety and effectiveness, and provides a promising and highly desired contraceptive alternative to oral contraception for young women.     

The alpha(2)beta(1) and alpha(3)beta(1) integrins do not mediate attachment of endometrial cells to peritoneal mesothelium

OBJECTIVE: To evaluate the possible role of mesothelial alpha(2)beta(1) and alpha(3)beta(1) integrins in the attachment of endometrial stromal cells (ESCs) and endometrial epithelial cells (EECs). DESIGN: In vitro study. SETTING: University medical center. PATIENT(S): Women of reproductive age (n = 26). MAIN OUTCOME MEASURE(S): Mesothelial cells were grown on collagen IV. Endometrial stromal cells and EECs were plated on mesothelial cells for 1 hour. Before plating, mesothelial cells or endometrial cells were incubated with antibodies to alpha2, alpha3, and beta1 integrin subunits. The effect of these antibodies on ESC and EEC binding to collagen IV and collagen I was also examined. The expression of collagen I, collagen IV, fibronectin, and laminin by cultured ESCs and EECs was examined. RESULT(S): The anti-integrin antibodies had no effect on endometrial binding to mesothelium. The beta1 integrin antibody decreased binding of ESCs and EECs to the collagen matrices. In culture, ESCs and EECs expressed collagen I, collagen IV, fibronectin, and laminin to varying degrees. CONCLUSION(S): The initial adhesion of ESCs and EECs to mesothelium is not mediated by beta1 integrins. In contrast, ESC and EEC attachment to collagen IV and collagen I, which are present in the submesothelial extracellular matrix, is mediated by beta1 integrins.     

Expression of progesterone receptors is significantly impaired in the endometrium of infertile women during the implantation window: a prospective observational study

Objective: To compare the expression of progesterone receptors (A?+?B) and type-B progesterone receptors in the epithelial and stromal cells of fertile and infertile women.

Methods: Women were divided into two groups, the group of fertile controls (group 1) and the group of infertile women (group 2) and were set on regular ultrasound imaging in order to detect ovulation. An endometrial biopsy was obtained on the seventh or eighth post-ovulatory day. Immunohistochemistry was performed to measure percentage of positive nuclei, intensity of staining and h-score for progesterone receptors (PgR) (A?+?B) as well as type-B progesterone receptors in epithelial and stromal cells. Secondary outcomes included endometrial tissue dating, the rate of tissues being out-of-phase and endometrial thickness.

Results: Endometrial issue was obtained from 15 fertile and 30 infertile women. Expression of PgR (A?+?B) and PgR type-B was significantly lower in the epithelial cells of infertile women. PgR (A?+?B) h-score was 220.0?±?18.5 for fertile versus 147.3?±?18.0 for infertile women (p?=?0.02). PgR type-B h-score in epithelial cells was 166.8?±?30.7 for fertile versus 90.8?±?20.6 for infertile (p?=?0.04). No significant difference was observed in stromal cells.

Conclusions: Expression levels of PgR (A?+?B) as well as type-B receptors are significantly lower in the epithelial cells of infertile women during implantation window.     

放置IUD后宫腔微生物及子宫内膜病理学研究

研究ＩＵＤ与盆腔感染及子宫内膜恶变或其他病理改变的关系,探讨 ＩＵＤ长期使用的安全性。方法：将 ８８例分为 Ａ、Ｂ、Ｃ、Ｄ ４组,Ａ组 ２０例使用带尾丝活性 ＩＵＤ;Ｂ组２４例使用惰性 ＩＵＤ;Ｃ组 ２４例为正常对照组;Ｄ组 ２０例为盆腔感染组。所有病例取宫腔冲洗液进行需氧菌、厌养菌、解脲支原体、沙眼衣原体等培养,并取子宫内膜进行病理学检查,结果：Ａ、Ｂ组主要表现为正常增生期、分泌期或月经期子宫内膜,部分是单纯性或腺囊性增生,与Ｃ组、Ｄ组差异无显著性（Ｐ＞０．０５）,４组均未见不典型增生及恶变。Ａ、Ｂ、Ｃ３组子宫内膜均无慢性炎症改变,Ｄ组８例存在慢性子宫内膜炎改变,与Ａ、Ｂ、Ｃ组差异有显著性（Ｐ＜０．０５）。Ａ、Ｂ、Ｃ组淋巴细胞、浆细胞、中性白细胞、纤维细胞计数差异无显著性（Ｐ＞０．０５）,Ｄ组淋巴细胞、浆细胞、中性白细胞计数较以上３组明显增加（Ｐ＜０．０５）,间质细胞及纤维细胞计数与以上３组差异无显著性（Ｐ＞０．０５）。Ａ、Ｂ、Ｃ组宫腔微生物检出率分别为３０．０％,２９．２％,２０．８％,与Ｄ组（７０．０％）差异有显著性（Ｐ＜０．０５）。结论：使用ＩＵＤ５－１４年未增加子宫内膜癌、癌前病变及慢性子宫内膜炎发生率。Ｉ     

CuIUD对妇女子宫内膜环氧化酶表达的影响

目的:　研究置固定式铜宫内节育器(FCuIUD)前后妇女子宫内膜组织中环氧化酶(COX-1、COX-2)的表达。方法:　选择符合受试条件的育龄妇女10 例,于月经净后3-7　d放置FCuIUD,置器前及置器后一个月于相同时期、相同部位刮取子宫内膜。RT-PCR法与Western　blot法分析放置FCu-IUD前后妇女子宫内膜组织COX-1、COX-2　mRNA及蛋白表达水平。免疫组化S-P法测定COX-2在子宫内膜的定位与分布。结果:置FCuIUD一个月后,子宫内膜COX-2　mRNA和蛋白表达水平均显著增加,与置器前比较,差异显著(P<0.05)。COX-1　mRNA及蛋白的表达在置器前后无明显差异。COX-2主要分布于腺上皮细胞的胞浆内。结论:　置FCuIUD后妇女子宫内膜COX-2表达在转录和翻译水平均显著增加;COX-2可能是节育器引起的无菌性炎症中PGs释放增加的主要同工酶。     

β1-Integrins Partly Mediate Binding of Ovarian Cancer Cells to Peritoneal Mesothelium in Vitro

Ovarian cancer cells frequently metastasize by implanting onto the peritoneal mesothelial surface of the abdominal cavity. Although the CD44 molecule expressed by ovarian cancer cells is known to partly mediate this process, the role of other adhesion proteins such as β1-integrins has been previously difficult to demonstrate using the 4B4 anti-β1 neutralizing antibody. In view of the widespread expression of β1-integrins in ovarian cancer, however, we have further examined the potential role of this class of molecules in ovarian cancer cell implantation through the use of an alternative anti-β1 neutralizing antibody, MAB13. We now report that MAB13 is capable of inhibiting the binding of three separate human ovarian cancer cell lines (36M2, CAOV-3, SKOV-3) to mesothelium (mean 37 ± 4% inhibition, n = 21, P < 0.001). An additive inhibitory effect was observed when MAB13 was combined with anti-CD44 antibody (clone 515) (mean 63 ± 3% inhibition, n = 19, P < 0.001), suggesting that binding occurs through two independent pathways involving both β1-integrins and CD44. Because fibronectin is an extracellular matrix ligand recognized by many types of integrins and is abundantly expressed on mesothelial cells, the inhibitory effects of MAB13 and 4B4 on ovarian cancer cell binding to fibronectin were directly compared. MAB13 inhibited ovarian cancer cell binding to fibronectin to a significantly greater degree than did 4B4, suggesting that the discordant effects of these two antibodies on mesothelial adhesion may be partly related to their differential ability to neutralizing fibronectin-mediated binding. Studies using anti-α5 neutralizing antibody demonstrated that the α5β1 fibronectin receptor contributes to approximately 50% of integrin-mediated binding of 36M2 and CAOV-3 cells (which express the α5 chain in 54 and 58% of cells, respectively). Since the RGD sequence of fibronectin is a known recognition site for many types of integrins, including α5β1 and ανβ3, we performed binding in the continued presence of both anti-α5 and RGD peptide in order to exclude other types of fibronectin–integrin interactions. The addition of RGD peptides at concentrations known to be capable of blocking fibronectin binding resulted in no additional inhibitory effect over that observed with anti-α5 antibody alone, suggesting that α5β1 was the major receptor responsible for fibronectin-mediated ovarian cancer binding to mesothelium. These data demonstrate that ovarian cancer cell binding to peritoneal mesothelium is mediated by several adhesion pathways and that simultaneous inhibition of both β1-integrin and CD44 function may be necessary in order to significantly limit the intraabdominal spread of this tumor in vivo.