HOXA10基因在子宫内膜异位症不孕患者内膜组织中的表达及意义

目的:探讨HOXA10基因在子宫内膜异位症(EMs)不孕中的作用及作用机制。方法:以行腹腔镜手术并经病理确诊为EMs合并不孕症的患者为研究对象(18例,A组),以同期行腹腔镜手术的输卵管性不孕患者(18例,B组)、正常生育组(15例,C组)为对照。分别应用荧光定量PCR、免疫组织化学和Western blotting等方法从mRNA及蛋白质水平检测HOXA10基因在EMs不孕症患者在位、异位子宫内膜以及对照组在位子宫内膜的表达。结果:HOXA10 mRNA及蛋白表达水平在C组的内膜较高;B组稍低于C组,但两者相比差异无统计学意义(P>0.05);A组的在位及异位内膜表达水平较C组明显降低(P<0.01);但A组的在位内膜与异位内膜基因和蛋白的表达水平均无统计学差异(P>0.05)。结论:HOXA10基因在EMs不孕患者在位子宫内膜中的表达显著降低,可能是EMs不孕患者子宫内膜容受性降低,进而引起不孕的重要因素之一。     

同源盒A10基因表达调控及其对子宫内膜异位症患者不孕的影响

正子宫内膜异位症(endometriosis,EMs)指子宫内膜组织(腺体和间质)出现在子宫体以外的部位,具有痛经和不孕等相关症状。EMs患者不孕的发生率是正常人的20倍,EMs不孕患者总数占不孕患者总数也高达30%~50%[1]。因此,EMs不孕症在不孕中具有重要地位。许多学者在EMs不孕的患者子宫内膜中检测到同源盒(homebox,HOX)A10基因表达显著下调,其受DNA甲基化、mi RNA异常表达、组蛋白乙酰化等表达调控影响。本文从HOXA10基因的结构、功能以及表达调控与EMs     

miRNA-135a对子宫内膜异位症HOXA10基因表达的调控的研究

目的:探讨miRNA-135a对子宫内膜异位症(EMs)中HOXA10基因表达的调控作用。方法:选取2013年1月到12月在天津市中心妇产科医院因EMs和单纯卵巢囊肿行腹腔镜手术的患者各80例。留取EMs患者的宫腔内膜组织(EMs在位内膜组)和异位内膜组织(EMs异位内膜组)以及单纯卵巢囊肿患者的宫腔内正常内膜组织。分别采用转染技术、实时荧光定量PCR技术检测miRNA-135a和HOXA10 mRNA的表达。结果:miRNA-135a和HOXA10 mRNA在不同月经周期表达水平不同。增殖期和分泌中期,EMs在位和异位内膜组织中miRNA-135a表达水平显著高于正常内膜,HOXA10 mRNA表达水平显著低于正常内膜,差异均有统计学意义(P0.01);EMs在位和异位内膜组织比较,差异均无统计学意义(P0.05)。经miRNA-135a、miRNA-135a抑制剂转染后,子宫内膜间质细胞中HOXA10 mRNA表达水平显著下降和升高,差异均有统计学意义(P0.01)。结论:EMs患者子宫内膜中HOXA10异常表达受miRNA-135a调控,miRNA-135a高表达抑制了HOXA10基因表达。     

SPOCK2基因表观失活在卵巢子宫内膜异位症恶变中的作用

目的 通过比较卵巢子宫内膜异位症(内异症)恶变患者的恶变组织、异位内膜组织和在位内膜组织中SPOCK2基因的甲基化及蛋白表达情况,探讨该基因的表观失活在卵巢内异症恶变中的作用.方法 选择2005年1月至2011年1月在中国医科大学附属盛京医院妇产科住院手术、并经术后病理确诊为卵巢内异症恶变患者22例的病理石蜡标本为恶变组(包括11例卵巢内膜样癌、8例透明细胞癌、2例浆液性囊腺癌及1例黏液性囊腺癌),以同期22例单纯卵巢内异症患者的异位内膜及在位内膜的病理石蜡标本(内异症组)及16例宫颈上皮内瘤变(CIN)Ⅲ患者的正常子宫内膜的病理石蜡标本(对照组)为对照.通过显微切割技术分别获取恶变组患者的恶变组织22份,癌旁异位内膜组织15份及在位内膜组织10份;内异症组患者的异位内膜组织22份及在位内膜组织17份;对照组患者的正常子宫内膜组织16份.通过亚硫酸盐修饰后酶切技术检测各组织中SPOCK2基因甲基化情况,免疫组化SP法检测SPOCK2基因的蛋白表达情况.探讨SPOCK2基因异常甲基化与其蛋白表达的关系.结果 (1)SPOCK2基因甲基化情况:恶变组患者的恶变组织中,SPOCK2基因甲基化发生率为45％(10/22),显著高于癌旁异位内膜组织(1/15),两者比较,差异有统计学意义(P＜0.05);恶变组患者的癌旁内异症组织中SPOCK2基因甲基化发生率(1/15)与内异症组患者的异位内膜(5％,1/22)比较,差异无统计学意义(P＞0.05).(2)SPOCK2基因蛋白表达情况:恶变组患者的恶变组织中SPOCK2基因蛋白表达缺失率为44％(11/22),显著高于恶变组患者癌旁异位内膜组织的2/15,两者比较,差异有统计学意义(P＜0.05);但恶变组患者癌旁异位内膜组织中SPOCK2基因蛋白表达缺失率(2/15)与内异症组异位内膜(5％,1/22)比较,差异无统计学意义(P＞0.05).3组在位内膜组织中SOPCK2基因的蛋白表达缺失率比较,差异无统计学意义(P＞0.05).(3)SPOCK2基因甲基化与其蛋白表达缺失的关系:SPOCK2基因异常甲基化能够导致其蛋白表达缺失( 20/22,P＜0.05).结论 SPOCK2基因的表观失活与卵巢内异症恶变相关.     

IL-10、IL-12在子宫内膜异位症组织中的表达

目的:检测IL-10、IL-12在子宫内膜异位症(EMs)患者在位内膜、异位内膜组织中的表达,为EMs发生发展机制的研究和临床靶向化治疗提供实验依据。方法:选取30例卵巢子宫内膜异位囊肿患者,取其异位内膜组织(EMs异位内膜组)和在位内膜组织(EMs在位内膜组)。选取同期在华北理工大学附属医院因其他原因行宫腹腔镜手术的30例患者的正常子宫内膜组织(对照组)。应用免疫组化法和Western blot法检测3组内膜组织中IL-10、IL-12表达。结果:与对照组比较,EMs组中IL-10表达升高,IL-12表达降低,差异均有统计学意义(P0.01)。EMs在位内膜中IL-10表达低于EMs异位内膜,IL-12表达高于EMs异位内膜,差异均有统计学意义(P0.01)。结论:EMs子宫内膜局部及种植部位中IL-12表达降低和IL-10表达升高与EMs的发生、发展有一定的相关性。     

HOXA10、HOXA11基因与子宫内膜异位症性不孕的研究进展

子宫内膜异位症(endometriosis,EMS)是不孕症的常见病因,HOXA10、HOXA11这2种基因的正常表达与子宫内膜分泌中、晚期容受性的形成关系密切,而这2种基因在EMS患者的子宫内膜中与正常人相比表达下降,故EMS不孕的主要机制可能为低表达的HOXA10、HOXA11这2种基因,使子宫内膜的蜕膜化异常、容受性下降。此外,近期研究指出,导致EMS患者HOXA10、HOXA11基因表达下降的主要因素可能是基因异常甲基化。     

子宫内膜异位症患者内膜容受性及“种植窗”的特点

子宫内膜异位症(EMs)通过多个环节影响女性生育能力和不孕的治疗效果。EMs合并不孕的患者其子宫内膜细胞学形态方面:胞饮突的表达量、内膜腺体数目、基质有丝分裂细胞数较健康对照组均显著减少,腺体的腺腔分布不规则,微绒毛少、纤毛再生不全、发育不良;分子生物学方面:种植窗期内膜整合素αvβ3减少,基质金属蛋白酶-9(MMP-9)、细胞外基质、激活素A、细胞黏附分子、芳香化酶P450、IgG和IgA抗体等多种细胞因子的异常;基因学方面:HOXA10、HOXA11基因呈低水平表达,MMP-2和MMP-9表达升高;类固醇激素17β-羟基类固醇脱氢酶(17β-HSDs)等不表达,从而降低EMs患者的子宫内膜容受性。促性腺激素释放激素激动剂预处理可有效提高EMs患者子宫内膜容受性。     

HOXA10基因在子宫内膜异位症患者在位及异位子宫内膜组织中的表达及其意义

目的 探讨HOXA10基因在子宫内膜异位症(内异症)患者在位及异位内膜组织中的表达水平及其临床意义.方法 选取2009年1月至2010年8月于佛山市妇幼保健院因内异症行腹腔镜手术治疗的患者30例,留取宫腔内膜组织(内异症在位内膜组)和异位内膜组织(内异症异位内膜组);同期因卵巢囊肿及输卵管因素不孕行腹腔镜手术治疗患者30例为对照组,留取宫腔内正常内膜组织.分别采用实时荧光定量PCR技术、免疫组化法和蛋白印迹法检测各组内膜组织中HOXA10 mRNA及蛋白表达水平.结果 内异症在位内膜组HOXA10 mRNA及蛋白表达水平分别为0.61±0.07和0.47±0.05,内异症异位内膜组分别为0.64±0.06和0.50±0.05,对照组分别为1.22±0.14和1.42 ±0.14;内异症在位和异位内膜HOXA10 mRNA及蛋白表达水平明显低于正常内膜中的表达水平,差异均有统计学意义(P均＜0.01);内异症在位和异位内膜组的HOXA10 mRNA及蛋白表达水平比较,差异则无统计学意义(P＞0.05).免疫组化法检测内异症在位和异位内膜组织的间质和腺细胞中HOXA10表达均降低.结论 HOXA10基因在内异症在位及异位内膜组织中均呈低表达状态,可能与内异症的发病和不孕有关.     

子宫内膜异位症DNA异常甲基化的研究进展

DNA甲基化是基因组表观遗传调控重要的方式之一.近年研究发现,DNA甲基化造成的相关基因异常表达在子宫内膜异位症发生发展中有着重要影响,尤其是HOXA10基因的异常甲基化导致其基因表达下降.回顾相关基因异常甲基化与子宫内膜异位症发生、诊断、治疗及预后判断的关系,进一步探讨子宫内膜异位症中可能的分子机制.     

子宫内膜异位症DNA异常甲基化的研究进展

DNA甲基化是基因组表观遗传调控重要的方式之一。近年研究发现,DNA甲基化造成的相关基因异常表达在子宫内膜异位症发生发展中有着重要影响,尤其是HOXA10基因的异常甲基化导致其基因表达下降。回顾相关基因异常甲基化与子宫内膜异位症发生、诊断、治疗及预后判断的关系,进一步探讨子宫内膜异位症中可能的分子机制。     

Laparoscopy for the treatment of unexplained infertility

Aim:  To determine the best treatment for unexplained infertility.
Methods:  A retrospective study was used to examine Japanese women with unexplained infertility that had undergone laparoscopy. The main outcome measure of the study was the rate of pregnancy after laparoscopy.
Results:  One hundred and thirty-eight women diagnosed with unexplained infertility received laparoscopy and as a result 55 women had their diagnosis of unexplained infertility confirmed. There were no statistically significant differences between the women who became pregnant after laparoscopy in terms of duration of infertility, duration of treatment or age. The pregnancy rate of women with unexplained infertility was 56.4%, with 90% of these pregnancies achieved within the first 6 months. There were 64 women with minor endometriosis considered to be suffering from unexplained infertility before laparoscopy. The characteristics of the patients in the unexplained infertility group and in the minor endometriosis group were similar, but patients with minor endometriosis were found to have a lower pregnancy rate compared to those with unexplained infertility (35.9% vs 56.4%; P  = 0.02).
Conclusions:  The effective period after laparoscopy appears to be 6 months. Assisted reproductive technology should be considered after that time. Pregnancy rates were low in women with minor endometriosis compared with unexplained infertility. It is important to clarify the cause of infertility using laparoscopy. (Reprod Med Biol 2006; 5 : 59–64)     

Endometriosis and the Infertile Patient

Approximately one-third of all patients who suffer from endometriosis may not be able to conceive. More than 10% of infertile patients have endometriosis as the causative factor of their infertility. The stressful effect of infertility on the couple's life may be devastating. The infertility and endocrinology nurse may play a major role in alleviating the painful experience of such unfortunate patients. The pathogenesis, pathophysiology, diagnosis, and therapy of endometriosis are described. The important role of the nurse in the management of patients with endometriosis is emphasized.     

阴道子宫内膜异位症18例临床分析

目的:探讨阴道子宫内膜异位症(内异症)的临床特点和治疗效果。方法:回顾性分析我院2003年1月至2005年10月收治的18例经病理证实为阴道内异症患者的临床资料。结果:阴道内异症独立存在者13例(72.2%),合并盆腔内异症者5例(27.8%)。前组性交痛及合并妇科良、恶性肿瘤的比例高于后组,而合并不孕的比例较后组低。所有患者中8例行保守性手术治疗,其中4例术后加用GnRHa治疗3个月;其余10例均行根治性手术治疗。平均随访18.6月,共有2例复发(11.1%),均见于肿块直径≥3 cm、行阴道局部切除未用药物治疗者。总共半年累积复发率13.3%(2/15),保守性手术复发为25%(2/8),其半年累积复发率40.0%(2/5);保守性手术术后加用药物治疗者及行根治性手术者无复发。各种术式之间比较,无明显统计学差异(P>0.05)。结论:阴道子宫内膜异位症与常见的盆腔内异症相比较,有其特殊之处。其发生机制可能与盆腔内异症不同,尚有待进一步研究。     

Peritoneal fluid from patients with endometriosis decreases sperm binding to the zona pellucida in the hemizona assay: a preliminary report.

OBJECTIVE: To evaluate the effect of peritoneal fluid (PF) from patients with endometriosis on gamete interaction under hemizona assay (HZA) conditions. DESIGN: The HZA was used to study the effect of PF from patients with endometriosis on sperm binding to the zona pellucida using media and normal PF as controls. SETTING: The patients were collected from a university hospital infertility clinic. PATIENTS: Peritoneal fluid from 16 women being evaluated for infertility or sterilization who were found to have endometriosis at surgery was used. Three normal patients, who were being sterilized, had PF that was used as a control. RESULTS: Results suggest that there is a significant reduction in the number of tightly bound sperm to the zona surface in endometriosis specimens as reflected in the hemizona index and that this effect is directly related to the stage of the disease. CONCLUSIONS: Although the sample is small, this methodology may help to elucidate one of the mechanisms responsible for endometriosis-associated infertility.     

Luteinized unruptured follicle in the early stages of endometriosis as a cause of unexplained infertility.

OBJECTIVE: We attempted to clarify the relationship between luteinized unruptured follicle, which occurs in the early stages of endometriosis, and unexplained infertility. STUDY DESIGN: Seventy patients who had unexplained infertility were reviewed. RESULTS: Laparoscopic examination showed that 47 patients (67%) had endometriosis; of these, 40 (85%) had minimal or mild disease. The incidence of luteinized unruptured follicle was higher (p < 0.05) in patients who had endometriosis (35%/patient and 25%/cycle) compared with patients who did not have endometriosis (11%/patient and 7%/cycle). Degenerated oocyte cumuli were collected in 6 (43%) of 14 luteinized unruptured follicles diagnosed by transvaginal ultrasound. CONCLUSIONS: These results show that luteinized unruptured follicle is common in patients who have mild or minimal endometriosis and that it may be one of the causes of endometriosis-associated infertility. Transvaginal ultrasound-guided follicular puncture of luteinized unruptured follicle during the mid luteal phase may be useful in establishing a definitive diagnosis of luteinized unruptured follicle.     

Importance portance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility

Objective: To determine whether reactive oxygen species in peritoneal fluid might be a factor in infertility.Design: Prospective study.Setting: Andrology laboratory and gynecology clinic at a tertiary care facility.Patient(s): Women with endometriosis (n = 15) or idiopathic infertility (n = 11) who under-went laparoscopy for infertility. Patients undergoing tubal ligation served as controls (n = 13).Intervention(s): Aspiration of peritoneal fluid.Main Outcome Measure(s): Reactive oxygen species levels, presence of polymorphonuclear granulocytes, and leukocyte distribution in peritoneal fluid.Result(s): Reactive oxygen species were present in the peritoneal fluid of patients with endometriosis, idiopathic infertility, and tubal ligation. Levels of reactive oxygen species did not show a statistically significant difference between patients with endometriosis and the control group in either unprocessed or processed (cell-free) peritoneal fluid, but did differ significantly between patients with idiopathic infertility and controls in process peritooneal fluid. Polymorphonuclear granulocytes (> 1 × 10⁸/mL) were not present in the peritoneal fluid of any patient. Macrophage concentrations of peritoneal fluid did not differ significantly between controls and patients with endometriosis or idiopathic infertility.Conclusion(s): Reactive oxygen species in the peritoneal fluid may not affect fertility directly in women with endometriosis; however, they may have a role in patients with idiopathic infertility.     

Transvaginal hydrolaparoscopy but not standard laparoscopy reveals subtle endometriotic adhesions of the ovary

OBJECTIVE: To determine whether transvaginal hydrolaparoscopy is superior to standard laparoscopy for detection of subtle endometriotic adhesions of the ovary. DESIGN: Videotapes of standard laparoscopy and transvaginal hydrolaparoscopy were viewed by an independent observer in random order and in a blinded manner. SETTING: Tertiary referral centers for infertility. PATIENT(S): Patients with minimal or mild endometriosis (n = 11) and unexplained infertility (n = 10) on standard laparoscopy from a group of 43 patients with infertility who were undergoing both studies. INTERVENTION(S): Transvaginal hydrolaparoscopy followed by standard laparoscopy. MAIN OUTCOME MEASURE(S): Detection of unexplained ovarian adhesions. RESULT(S): Patients with minimal and mild endometriosis and unexplained infertility had significantly more ovarian adhesions on transvaginal hydrolaparoscopy than on standard laparoscopy. The subtle adhesions seen on transvaginal hydrolaparoscopy but not on standard laparoscopy were filmy, microvascularized, and nonconnecting. CONCLUSION(S): Unexplained ovarian adhesions are frequently detected on transvaginal hydrolaparoscopy but not on standard laparoscopy in infertile patients with minimal and mild endometriosis and unexplained infertility.     

Ovarian cancer risk associated with varying causes of infertility

OBJECTIVE: To evaluate the risk of ovarian cancer as related to underlying causes of infertility. DESIGN: Retrospective observational cohort study. SETTING: Five large reproductive endocrinology practices. PATIENT(S): A total of 12,193 women evaluated for infertility between 1965 and 1988. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian cancer ascertained through 1999. RESULT(S): With 45 identified ovarian cancers, this cohort of infertility patients demonstrated a significantly higher rate of ovarian cancer than the general female population (standardized incidence ratio [SIR] = 1.98; 95% confidence interval [CI], 1.4-2.6). The risk was higher for patients with primary infertility (SIR = 2.73) than for those with secondary infertility (SIR = 1.44), and it was particularly high for patients who never subsequently conceived (SIR = 3.33). Women with endometriosis had the highest risk (SIR = 2.48; 95% CI, 1.3-4.2), with a further elevated risk among those with primary infertility (4.19, 2.0-7.7). Comparisons among the infertile women, which allowed calculation of rate ratios (RRs) after adjustment for multiple factors, also showed links with endometriosis. Compared with women with secondary infertility without endometriosis, patients with primary infertility and endometriosis had a RR of 2.72 (95% CI, 1.1-6.7). CONCLUSION(S): Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes. Further study of endometriosis may provide insights into ovarian carcinogenesis.     

Association of endometriosis and spontaneous abortion: effect of control group selection

Endometriosis has been associated with an increased incidence of spontaneous abortion, compared with the abortion rate of the general population. To assess whether a separate control group would affect these conclusions, we studied 139 consecutive infertility patients with laparoscopically proven endometriosis to determine the incidence of spontaneous abortion. Ninety-five of these patients underwent conservative surgical resection of endometriosis, and 44 patients opted for expectant management. There was no significant difference between these two groups in average age, duration of infertility, or proportion of patients with primary infertility. The average spontaneous abortion rate before diagnosis for all patients was 63.1%. After surgical treatment, the abortion rate dropped to 0% (P less than 0.000001) for all stages of disease. However, even in those patients who received expectant management only, the abortion rate fell to 16.7% and 21.4% for mild and moderate endometriosis, respectively (P less than 0.001). These results suggest that the spontaneous abortion rate in untreated endometriosis may not be as high as previously reported and may not be significantly different from the rate in the general population. The data also emphasize the need for well-defined control groups when assessing the effects of a treatment regimen.